The overall goals of this line of research are to treat chronic cigarette smokers and to understand the processes related to smoking and relapse in these smokers. Combined treatment with antidepressants, nicotine replacement therapies (NRT), and psychological intervention produces high initial abstinence rates. Our ongoing work suggests that extended treatment can maintain these rates, achieving abstinence rates greater than or equal too 60% at one year. A series of hypotheses about the efficacy of extended antidepressant treatment and an empirically based behavioral relapse prevention intervention will be tested. There are five experimental conditions. Chronic smokers (N=400) receive 12 weeks of combined pharmacological treatment (sustained release bupropion + nicotine patch) and psychological intervention, and then are randomly assigned to one of five conditions in a placebo-controlled, double-blind design: (1) 40 weeks active bupropion with medical management (Active/MM); (2) 40 weeks placebo drag with medical management (Placebo/MM); (3) 40 weeks bupropion + behavioral relapse prevention (Active/RP); (4) 40 weeks placebo + behavioral relapse prevention (Placebo/RP); (5) no farther treatment (Brief Treatment). The innovative behavioral relapse prevention intervention will focus on five areas generally agreed to be important post-cessation. These are fluctuating motivation, depression, withdrawal/dependence, weight gain and social support. Participants will be assessed at baseline on smoking behavior, nicotine dependence, psychiatric diagnosis, demographics and measures of anger, anxiety, depression, mood disturbance, social support, stress, health status, motivation for change, and drug and alcohol use. At weeks 12, 24, 36, 52, 64, and 104, participants will be assessed on self-reports of smoking verified by carbon monoxide and anatabine/anabasine assays, as well as on psychometric measures. The proposed research will address significant issues in the treatment of poor prognosis smokers, including the development of strategies to maintain abstinence, determination of the efficacy of extended pharmacological treatment, and determination of the efficacy of a behavioral relapse prevention intervention.