Psychiatric patients studied early during treatment with chlorpromazine and thioridazine demonstrated elevated probenecid-induced accumulations of homovanillic acid, a major dopamine metabolite, in cerebrospinal fluid. In those studied after longer periods of treatment with phenothiazines, homovanillic acid values were not elevated. This suggests that there are time-dependent effects of phenothiazines on dopamine turn-over that may be relevant to the time course of antipsychotic efficacy.