The aim of the present study was to replicate earlier findings of beneficial effects of ORG 2766, an ACTH-(4-9) analog, in autistic children. Fifty children with autism, 7-15 years old and with a Performance IQ of more than 60, participated in a double-blind placebo controlled parallel trial. Active treatment was 40 mg ORG 2766 for 6 weeks. The outcome was assessed on the basis of the Aberrant Behavior Checklist completed by parents and teachers, and by means of a detailed behavioral observation (30 subjects). ORG 2766 failed to improve social and communicative behavior at a group level. The rate of individual response, defined as a reliable change in social withdrawal at home and at school, to ORG 2766 (10 out of 30) and placebo (4 out of 20) was not significant either. The children who responded to ORG 2766, but not those who responded to placebo, manifested significant improvements outside the changes in the defining variables, including a decrease in hyperactivity at school. The responders to ORG 2766 were characterized mainly by a relatively lower PIQ; further by more initial hyperactivity, stereotypies and abnormal speech, and less initial eye contact. The responders to placebo could not be differentiated from the non-responders to placebo. Future studies should examine whether ORG 2766 differentially affects various subtypes of autism.