Piquindone (RO22-1319), a new "atypical" neuroleptic, was administered for 2 weeks to 37 schizophrenic patients, and the effects of treatment were examined in a double-blind, placebo-controlled trial. "Atypical" neuroleptics are those that block animal behaviors that model antipsychotic actions in humans at doses lower than those necessary to block animal behaviors that model extrapyramidal actions. Our results demonstrate that piquindone led to moderate but significant improvements in the positive symptoms of schizophrenia and to improvements in negative symptoms just below the level of statistical significance. This supports the notion that neuroleptics categorized as "atypical" in preclinical experiments may prove to be clinically efficacious in humans. In addition, our anecdotal observations were that piquindone caused minimal extrapyramidal symptoms. This is consistent with the preclinical data and suggests that atypical neuroleptics may be associated with fewer extrapyramidal side effects in humans than conventional neuroleptics. However, this must be substantiated by further research.