1. We have reviewed a group of 25 cases of mental disease (Danvers State Hospital material), so selected as to offer a fair sample of mental diseases arising in the fifth decade of life.2. Our principle of selection excluded all cases which were obviously not characteristic of the fifth decade (paresis, alcoholic mental disease, and the like); the group of non-characteristic cases thus excluded was extremely large (approaching So per cent of all cases arising in the decade) and the preventable diseases alone amounted to over 60 per cent.3. We remained with a group of 25 cases (10 males and 15 females) which present certain common aspects. These cases may be negatively defined as not due to syphilis, alcohol, cerebral arteriosclerosis, brain atrophy, or other factors yielding coarse brain disorder; as not possessing pronounced schizophrenic features; as not uniform in course or outcome; as not likely to show either elation or expansive delusions. They may be positively defined as almost, if not quite, constantly subject to delusions at some stage in each case; as yielding manic-depressive traits in the large majority of cases; as prone to depressive features; as possessing a strong hereditary taint (74 per cent of properly studied cases); as not infrequently suggesting disorder of glands of internal secretion.4. The delusional features, present in all cases (save one of myxedema), were not characteristically of any particular form; the delusions were somatic in 14 cases; dealt with various alterations of personality in 14 cases (combined with somatic delusions in 8 instances); and (superficially at least) dealt with the social environment in 13 cases (6 times combined with other forms).5. As to somatic delusions, it is further of note that a physical basis could be recognized for many of them in diseases of the viscera; and that, on the whole, these visceral counterparts of the delusions were more serious than the patients' complaints themselves.6. Delusions of negation (5 instances) and of unreality (4 cases) do not bulk so large statistically as they are apt to in descriptions of so-called involution-melancholia.7. The group, taken as a whole, is far more suggestive of manic-depressive insanity than of dementia præcox or of any other form of mental disease.8. On the whole, depression is the most common manic-depressive feature of these cases: but the constant occurrence of various delusions alongside the depressive emotions makes the latter seem far from "causeless," certainly not so causeless-looking as the depressions of manic-depressive insanity.9. It cannot be dogmatically asserted; but, on the whole, these patients seem more dominated by various ideas and by various more or less false beliefs than are the manic-depressives of earlier decades, and are perhaps more victims of intellectual than of emotional or volitional disorder. However, this may be more appearance than reality, and further work may again pull the emotions, and particularly the depressive emotions, into the genetic foreground.10. As to the designation "involution-melancholia" for these cases, it may be surmised that the term was adopted by alienists having unpleasant delusions at least as much in mind as unpleasant MERE emotions. Perhaps it is unwise to seek to overthrow the classical term before more intensive work has been done on the actual relation of the intellect to the emotions in this group: how far then, it may be asked, is the melancholia of involution merely systomatic and responsive to intellectual conditions?11. Since Freud has claimed a sexual basis for paranoia and even perhaps for paranoic states falling short of paranoia, it is fair to inquire how far the present group has a sexual basis: three of the fifteen female cases in our series harbored rather systematic delusions of persecution, and all three systems had a sexual tinge. This fact, allocated with the not infrequent tendency to disorder of glands of internal secretion in certain cases, ought to provide a fruitful field for psychoanalytic hypotheses.12. Hallucinations, as a rule auditory, were observed in something like 60 per cent to 70 per cent of the cases: there are á priori reasons (Wernicke) for relating these with the unpleasant delusions characteristic of the group; but, whether the false beliefs irradiate over to incite the hallucinations, or whether the hallucinosis is a prime factor in producing the false beliefs, must remain an open question: statistically we should be forced to favor the former process.13. The post mortem data throw some light on the negative definition of our group (see paragraph 3 supra). There appears to be little or no evidence that the metabolic disorder, if there be such underlying this group, tends to brain wasting.14. Our study of the distribution of certain chemically ill defined lipoids (or pigments, as we have called them) shows that age plays some part in the amount of deposits, perhaps more in the neuroglia cells than in the nerve-cells, and least of all in the perivascular phagocytes.15. All cases living three years or more after onset of symptoms show more or less marked accumulations of pigment in neuroglia cells; the same cases show a greater variability in the nerve-cell accumulations; occasionally such a three-year or over-three-years case will show a negligible amount of pigment in perivascular phagocytes.16. These pigment-findings are in substantial agreement with those of Southard-Mitchell, 1908:(a) "Perivascular cell pigmentation almost uniform in different areas of the same case." The present series presents only two instances of marked variability from area to area.(b) "Neuroglia cell pigmentation * * * varies more or less directly with age." Our present group presents more variation than did the former; there is however no absolutely negative case over 46 years of age.(c) "Nerve-cell pigmentation is not a function of age." Two cases of 50 years or more showed no appreciable amount of pigment, and three others showed but slight amounts. The variations in amount within a given brain are more striking than the variations shown by the neuroglia cell pigments.17. That these three loci for the deposition of pigment tend at last to a species of saturation is indicated by the fact that the even degrees of moderate or of marked pigment deposit in all loci begin to appear in the later years of life (one case at 49 years, one at 56, and the rest from 59 to 75 years).18. The fresh point of view thus obtained for the problem of involution-melancholia by our study of fifth-decade insanities may be stated as follows:Involution- melancholia has been regarded as possibly akin to manic-depressive insanity or even identical therewith or as possibly something quite different. Perhaps the majority of psychiatrists would regard it as a disease akin to manic-depressive insanity but modified by climacteric or presenile changes and distinguished from manic-depressive insanity by the peculiar tendency to depressoin which has given it its name. The novel feature of our investigation has been to study the age-factor. We have studied unselected cases arising in the fifth decade of life, excluding all coarse organic cases of brain lesion. Our resultant group is, we believe, although small, otherwise ideally representative of the conditions underlying mental disease at this age-level. Our group includes a sufficient number of the familiar cases of involution-melancholia as well as cases of delusional insanity without melancholia. The striking fact is that the melancholia cases prove also delusional. In so far as our group is representative of the fifth decade, we believe that the essential psychopathia involutionis is characterized by delusions, that in the large majority of cases melancholia is a feature superadded to the delusions, and that in a smaller majority of cases hallucinosis also occurs. The fact that melancholia may assert itself as the most prominent symptom in the clinical foreground fails to controvert the possible genetic importance of the delusions. As to the cause of psychopathia involutionis, it is easy to invoke the glands of internal secretion; and of their disorder there is actually some sign in a number of cases. Whether such disorder or some unknown factor determines the over-pigmentation (lipoid accumulations) in the cortex above noted, and whether these deposits have a direct relation to the symptoms must rest with the future.