In an open clinical trial the azepine derivative B-HT 920 was administered to patients with schizophrenia, paranoid type (according to ICD-9 and DSM-III criteria), in order to examine whether dopamine autoreceptor stimulation exerts antipsychotic effects. Twelve patients participated in the study and received the test drug orally for up to 28 days in a dose range from 0.3 to 1.2 mg/day. The following results emerged: in four patients a significant amelioration (reduction of initial BPRS scores by more than 50%) of psychotic symptomatology was observed; eight patients remained without improvement of psychopathology. Psychomotor activation was observed in seven patients, and prompted termination of the trial in two cases. No other marked adverse effects of B-HT 920 were noted, including EEG, ECG, and clinical chemistry parameters. As it was to be expected from the pharmacology of B-HT 920, plasma prolactin concentrations were significantly reduced two hours after oral application of a single dose of the drug. It remains to be clarified whether chronic treatment with B-HT 920 induces antipsychotic efficacy within as yet unidentified subsamples of schizophrenic patients. The observed activating effects of B-HT 920 may focus future investigative efforts toward study samples where negative symptoms predominate.