Based on reports that opiate antagonists can curtail short-term eating in several species including humans, the efficacy of naltrexone in promoting weight loss by obese subjects was examined. Naltrexone, a long-acting oral opiate antagonist, was studied in a randomized parallel double-blind placebo controlled ten week trial in 27 females and 14 males who were 30-100 percent overweight. Subjects on naltrexone lost an average of 1.8 kg and placebo subjects lost 1.5 kg, with no significant difference between groups. Three subjects who took naltrexone had elevations of liver transaminases, two times higher than normal. In the present study naltrexone at a daily dosage of 200 mg did not appear to have efficacy in producing weight loss after eight weeks of treatment. Studies of the effects of naltrexone at higher dosage or for longer periods should monitor hepatic function.