The efficacy of intramuscular pipothiazine palmitate (PP) in the management of aggressive mentally handicapped patients was examined in a double-blind, placebo-controlled, cross-over study, in which 30 patients received each treatment for 13 weeks. A target symptom scale of aggressiveness (TSA) and a clinical global impression scale of efficacy were rated at monthly intervals, and an extra-pyramidal side-effects scale weekly. The patients showed marked improvement during treatment with PP, which was assessed as superior to placebo. Individual and total TSA scores were also reduced compared to placebo.