This open pilot study explored the efficacy and safety of pimozide, over a 3-week period, in hospitalized autistic children. Eight males, ages 4.2 to 8.3 years, completed the study. Intellectual functioning ranged from moderate to profound mental retardation. Symptoms included severe withdrawal, stereotypies, hyperactivity and/or hypoactivity, aggressiveness, and temper tantrums. Therapeutic daily doses of pimozide ranged from 3.0 mg to 6.0 mg with a mean of 4.9 mg (0.12-0.32 mg/kg; mean, 0.22). Laboratory studies including electrocardiogram and liver function tests remained within normal limits. Untoward effects were minimal and transient. Decreases of behavioral symptoms were evidenced on all measures including the Children's Psychiatric Rating Scale, Clinical Global Impressions, and Global Clinical Judgments Scale (consensus rating). Of the 5 hypoactive children, 4 showed a decrease in hypoactivity, whereas 1 child showed worsening. These findings are promising and indicate the need for further study.