Fenfluramine therapy has been reported to improve behavior in infantile autism and has been associated with a decrease in abnormally increased blood serotonin content. The primary central effect has not been proved to be serotonergic. Beta-endorphin is involved in the anorexic effect of fenfluramine and may play a role in autism. Nine children with infantile autism were treated with fenfluramine in double-blind, placebo-crossover design. Transient anorexia was the only adverse effect. Autistic behavior was reported to improve in three patients, but objective psychometric tests were unchanged. Beta-endorphin-like immunoreactivity was determined in lumbar cerebrospinal fluid of patients during and before or after treatment with fenfluramine and then was compared to normal controls. Beta-endorphin was elevated significantly in the baseline autistic group (p less than .005) and was reduced toward control values during fenfluramine treatment. The results are consistent with a role for beta-endorphin in infantile autism and in the mechanism of fenfluramine treatment.