Fenfluramine, a serotonin reducing agent, has been the subject of intense research effort in recent years. A variety of biochemical studies summarized suggest that some autistic children and many nonautistic severely retarded individuals have elevated blood serotonin concentrations. The research on fenfluramine's clinical efficacy is thoroughly reviewed from a methodological perspective. All studies assessing the drug's effects on blood serotonin have observed reductions in whole blood serotonin to about 50% of baseline concentrations. Although there were early reports of drug enhancement of IQ, there is no good evidence that this is the case. However, there are data to suggest that fenfluramine may enhance social relatedness, reduce stereotypic behavior, lessen overactivity, and improve attention span in some autistic children, although these results do not appear consistently across studies. The animal literature on the neurotoxicity of fenfluramine is reviewed, and a number of limitations in this research are identified that raise questions about its relevance to the pharmacotherapy of children.