Response to dextromethorphan (15 mg b.i.d.), an antitussive agent not usually considered to have psychotropic properties, was seen in a 25-year-old man with severe developmental disabilities, congenital rubella, and an organic mental disorder. Dextromethorphan affects CNS serotonergic systems, and this was the probable therapeutic mechanism. This and other published cases suggest the existence of a distinct organic mental syndrome in developmentally disabled persons which responds to drugs that increase indoleaminergic activity.