Current pharmacological treatments for smoking cessation including nicotine replacement therapies and buproprion, are modestly successful in assisting smokers to quit. However, new treatments are needed. In particular, the problem of weight gain with smoking cessation is only partially reduced by current therapies. Furthermore, treatments that might address the link between alcohol consumption and smoking relapse may be particularly useful since many smokers are heavy drinkers, and this subgroup is particularly resistant to treatment. Based on our preliminary studies, we hypothesize that naltrexone, an opioid antagonist approved for the treatment of alcohol dependence, may be useful in augmenting the efficacy of transdermal nicotine replacement on rates of continuous abstinence and in preventing weight gain with smoking cessation. In the proposed study, we will test this hypothesis in 400 smokers seeking to quit smoking. All subjects will receive nicotine replacement therapy, and will be randomized to receive one of four doses of naltrexone (0, 25 mg, 50mg, or 100 mg daily) for six weeks following their quit date. Primary outcomes will be continuous abstinence during the last four weeks of treatment and weight gain. Secondary outcomes will include measures of craving for cigarettes, sweet and rich foods, and alcohol use. Through a careful analysis of data collected during the first week following their quit date, we will evaluate whether naltrexone treatment reduces the probability of continued smoking following their quit date, we will evaluate whether naltrexone treatment reduces the probability of continued smoking following a lapse in abstinence and the relationship between alcohol consumption and smoking relapse. A secondary aim of the study will be to explore predictors of response to treatment, including biochemical and neuroendocrine measures (e.g., baseline cotinine, naltrexone metabolite levels, cortisol levels), demographic characteristics (e.g., age/sex) and alcohol use history.