This preliminary study evaluated the potential efficacy of 50 mg of opioid antagonist naltrexone or placebo in combination with nicotine replacement therapy for smoking cessation, in a small sample of 32 smokers using one to one and a half packs of cigarettes per day. Addition of naltrexone resulted in an increase in continuous abstinence rates (9/16 for naltrexone vs. 5/16 for placebo). Naltrexone reduced the likelihood of relapse among participants who smoked during the first week of treatment, reduced desire to smoke, and prevented weight gain following smoking cessation. These preliminary results suggest that naltrexone augmentation of nicotine patch therapy using procedures designed to optimize the concurrent use of these two medications may be beneficial for smoking cessation.