We assessed the clinical and biological effects of high-dose, long-term Naltrexone (NTX) treatment in 11 children (3-11 years), who had been diagnosed as autistic. The drug was given following an open design, for 12 weeks. Beta-Endorphin (beta-END) was assayed in peripheral blood mononuclear cells after 1 and 3 months of treatment, and 6 months after the completion of the course. Baseline beta-END levels were higher than in healthy age-matched controls. In seven patients treatment reduced beta-END, whose levels rose in four children. Autistic symptoms were considerably attenuated in all cases, with functional improvements involving several areas. There was a close correlation between the reduction in beta-END levels and the decrease of social withdrawal, and an evident--though weak--correlation between increases in beta-END and decreases in stereotypy and abnormal speech. Both effects persisted after treatment stopped.