L-5-Hydroxytryptophan (L-5HTP) and the peripheral decarboxylase inhibitor carbidopa were administered to chronic schizophrenic patients in three separate experiments using a double-blind placebo-controlled crossover design. The three experiments were: (i) L-5HTP administration to 15 patients who had been withdrawn from all neuroleptic medication; (ii) L-5HTP administration to seven patients maintained on haloperidol; (iii) L-5HTP administration to nine patients maintained on chlorpromazine. Although the groups were diagnostically homogeneous, individual responses were highly variable. Considering each group as a whole, the only significant changes in rated psychosis consisted of an increase in the first group consequent to coming off neuroleptic medication and an increase in psychosis scores associated with adding L-5HTP to chlorpromazine. Neuroleptics apparently sensitize the central nervous system to the effects of L-5HTP loading. Acute exacerbations of psychosis induced by L-5HTP can be reversed by neuroleptics. Our experience does not give encouragement to the hypothesis that schizophrenic illnesses arise consequent to a deficit of serotonergic function that can be treated by giving a serotonin precursor in pharmacological quantities.