Buspirone is a novel antianxiety agent with no chemical similarity to other psychotropic medications. Pharmacological effects include inhibition of serotonin neurons, decrease of striatal levels of serotonin and metabolites, and reduction in serotonin binding sites. Buspirone also has effects on dopamine, norepinephrine, and the GABA systems. To pursue an antiserotonergic treatment rationale for autistic disorder, an open-blind 4-week trial comparing buspirone to fenfluramine or methylphenidate was conducted. Hyperactivity was a target symptom in three children with improvement noted in two with buspirone. Behavioral toxicity was encountered in one of two autistic subjects treated with methylphenidate and very mild improvement in another subject on fenfluramine. An autistic child with obsessive ideation was unchanged. No adverse reaction to buspirone was encountered. Further investigation in a double-blind trial of buspirone is warranted for treatment of symptoms of autism, especially aggression and hyperactivity.