A re-orientation to theory and therapy of some depressive states is slowly coming into sharper focus. The sequence of events developing from the response of a depressed patient to nicotinic acid and its relation to iproniazid is presented. Psychic energizers, mono-amine oxidase inhibitors, serotonin, and nor-epinephrine may have etiologic relationship in depressive disorders. Neurophysiological findings must also be integrated with psychopharmacological researches. A more specific nosological re-classification to recognize that involutional melancholia, manic-depressive states, and reactive depression may vary qualitatively rather than quantitatively is in order. Clinical experience with phenelzine (W-1544-A), a new mono-amine oxidase inhibitor, is presented as to drug characteristics, dosage, side effects, therapeutic effect, and comparability with iproniazid. In a preliminary screening at the private practice level, 69% of 36 patients who completed more than 4 weeks of treatment with W-1544-A showed remission from endogenous depressive states.