1. Skin histamine, releasable on intradermal injection of curare, and tolerance to intradermally injected histamine have been studied in 291 mental patients and 51 normal subjects.2. The data were analyzed statistically for the effect of sex, age, duration of hospitalization, drug treatments and diagnosis. Data from patients were also compared with normal subjects.3. Releasable skin histamine was the same in male and female patients but tolerance to histamine was greater in males.4. Age did not affect releasable skin histamine levels except in the 50-59 year old group as compared with the over 60 group. The difference was not striking but indicated a trend toward less skin histamine in the older age group. Tolerance to injected histamine was not affected by age.5. Duration of hospitalization, which may be a rough approximation of duration of mental illness did not alter skin histamine content or tolerance to histamine.6. Reserpine lowered skin histamine very considerably and was unique among the tranquilizing drugs in this property. Both reserpine and chlorpromazine increased the tolerance to histamine.7. Schizophrenics and manic-depressives did not differ in skin histamine levels or response to intradermally injected histamine.8. Patients receiving reserpine therapy had a lower level of skin histamine than normals, but patients not receiving drugs and patients receiving drugs other than reserpine did not differ from normals in releasable skin histamine. Histamine tolerance was greater in patients receiving drugs in general, or reserpine in particular, than normal individuals. Normal individuals and patients not receiving drug therapy gave similar responses to intradermally injected histamine.9. An hypothesis is suggested for reconciling the infrequency of allergic reactions in psychotics with essentially normal releasable skin histamine and normal tolerance to intradermally injected histamine.Abstract Teaser