In the present open study the effects of the D1-dopamine antagonist SCH 39166 on positive and negative symptoms of schizophrenia (DSM-IIIR) were investigated. SCH 39166 was given orally according to a fixed dosage schedule (day 1: 25 mg b.i.d; day 4: 50 mg b.i.d.; day 7: 100 mg b.i.d.; day 18: 200 mg b.i.d.; day 21: 225 mg b.i.d.). Seven patients completed 2 weeks, and five patients completed the study. The reason for premature withdrawal was lack of efficacy or refusal to take SCH 39166. In none of the patients a reduction of the BPRS or CGI score was found. As measured with the PANSS, a significant reduction was observed in the score of the negative subscale, whereas the positive symptoms scale and general psychopathology score remained unaffected. Akathisia, rigidity and hypokinesia were reported occasionally, although only mild in severity. The results of the present study do not support the hypothesis that D1-dopamine antagonists are clinically effective antipsychotics in schizophrenia, considering the fact that SCH 39166 had no effect on positive symptoms. The present study provides circumstantial evidence for an effect of SCH 39166 on negative symptoms.