A 6 week double-blind placebo-controlled trial of cyproheptadine augmentation of ongoing haloperidol treatment was conducted in 40 chronic schizophrenic in-patients. Cyproheptadine augmentation, compared to administration of haloperidol with placebo, did not produce a statistically significant improvement in psychotic symptoms. Cyproheptadine augmentation caused significant reduction in the extrapyramidal symptoms, which supports the atypical profile of antipsychotics. As to the neuroendocrinological effect, cyproheptadine augmentation did not reduce the plasma prolactin level but did induce a decrease in the plasma cortisol level. Although long-term follow-up studies are needed to confirm the results, this study suggests that cyproheptadine augmentation may be effective in treating chronic schizophrenic patients who are intolerant of extrapyramidal side effects of conventional antipsychotics.