The antipsychotic efficacy of tiaspirone, a new atypical antipsychotic agent, was compared to standard neuroleptics, in a single-blind cross-over study. Nine actively psychotic schizophrenic patients entered the study and 6 completed it. Significant overall improvement, on BPRS and CGI ratings, occurred by week 4, on both--tiaspirone and standard neuroleptics. There were no significant differences between tiaspirone and standard neuroleptics, in their antipsychotic efficacy. In keeping with the preclinical profile of tiaspirone, no extrapyramidal symptoms (EPS) were observed with tiaspirone. Two patients showed EPS on standard neuroleptics. Five of the 6 patients showed mild transient elevation of liver enzymes while on tiaspirone. Liver enzymes returned to normal within 3 weeks of discontinuation of tiaspirone. Tiaspirone appears to be a promising new antipsychotic agent that may be clinically effective without causing extrapyramidal syndromes.