Compared the therapeutic effects of a new phenothiazine derivative, mesoridazine, with those produced by chlorpromazine in 55 patients in a state hospital. 29 Ss were treated with mesoridazine and 26 with chlorpromazine. The relative effects of the 2 agents were judged by evaluation of psychological change with emphasis on target symptom ratings, a global estimate of drug effect, occurrence of side effects, and various laboratory tests. Mesoridazine and chlorpromazine were both safe and effective antipsychotic agents. The effects of the two drugs could be differentiated, however, in that more severely ill Ss responded significantly better to treatment with mesoridazine than chlorpromazine. This difference in effect appeared in an analysis of significant regions for the aggregate Brief Psychiatric Rating Scale (BPRS), 6 BPRS symptoms, and 2 BPRS factors. The symptoms most responsive to mesoridazine suggest that it is particularly effective in the treatment of thought disorders commonly encountered in schizophrenia.