On the basis of literature data relative to the alteration of beta-endorphin tone in obese subjects, we conducted a clinical trial employing Naltrexone (a receptorial antagonist of endogen opioids) in order to evaluate its efficacy in increasing the compliance of these subjects on dietary treatment. The drug dosage was 50 mg/daily (100 mg/die). The clinical study was carried out following the double-blind crossover method for a period of 4 months in a group of 17 obese subjects who also underwent to psychodiagnostic interviews. Significant weight reduction was observed in the 9 patients who carried out the treatment by assuming Naltrexone (kg 4.00 +/- 3.97) rather than with placebo (kg 0.96 +/- 4.95). The drug was subjectively well tolerated and it did not alter the endocrine, metabolic, psychometric, and cardiovascular monitored parameters. The insulin secretion during OGTT did not show significant alterations. Our data emphasize the Naltrexone efficacy in improving the compliance of the obese subjects during dietary treatment.