There is considerable evidence that antagonism of the endogenous opioids will suppress food intake in a variety of animal species. The authors report a double-blind, placebo-controlled trial of the long-acting, orally active narcotic antagonist naltrexone in the promotion of weight loss in obese male subjects who were also undergoing dietary counseling for weight reduction. Subjects received medication (naltrexone, 300 mg/day or placebo) for 8 weeks following an initial 2-week single-blind placebo phase. The results failed to demonstrate an advantage for the active drug. However, the naltrexone was associated with hepatotoxicity when used at this dosage in this population.