The experiments here reported were designed to test the hypothesis that, unlike nonpsychotic subjects, patients with chronic schizophrenia do not develop tolerance to N,N-diethyl-D-lysergamide tartrate (LSD-25)—a hypothesis which, if confirmed, would indicate that this disorder is associated with a defect in some mechanism of tolerance to normal, but potentially toxic products of metabolism, rather than to abnormal production of some as yet unidentified toxin. Cholden et al1 had already reported that in chronic schizophrenic patients grossly observable changes in behavior do occur after intramuscular injection of a single dose of LSD-25 (100μg total) and that such effects are no longer observed after once-daily repetition of this dose for three days or even after progressive increase of the daily dose to 500μg over a period of five days, but we were not aware of their findings until after our experiments had been completed.