The vast majority of attempts to quit smoking end in failure due to many reasons including the presence of aversive withdrawal symptoms. Given the health consequences of continued smoking, treatment ineffectiveness leads to substantially elevated morbidity and mortality, with immense financial and human cost. One of the commonly reported symptoms, sleep disturbance by itself, can act as an amplifier of many of the other symptoms, as sleep disturbance in other medical conditions and in experimental situations has been found to produce dysphoria, difficulty thinking, and drowsiness. Bupropion, an agent effective in assisting smoking cessation, also has sleep disturbance as a commonly identified self-reported side effect with prevalence estimates of from 30-50 percent among quitting smokers. Likewise, the use of transdermal nicotine is associated with reported sleep disturbance, especially when used over 24 hours. Combination treatment of bupropion and transdermal nicotine has been shown to produce sleep disturbance in nearly 50 percent of cases, compared to 20 percent of quitting smokers using a placebo. The world' s literature on smoking cessation and objectively measured sleep disturbance is based on fewer than 80 subjects. We propose to utilize a randomized, four-group design with repeated measurements of withdrawal and sleep disturbance to evaluate the effect of smoking cessation following treatment with behavioral counseling in combination with either placebo bupropion and nicotine patch, active bupropion, active patch, or combined active bupropion and patch in male and female smokers. Subjects will be followed for a period of twelve months to determine abstinence (confirmed by expired-air CO). A key aspect of the research design is the use of newer definitions of arousal that may more accurately reflect the true extent of sleep disruption following smoking cessation. The specific aims are to: 1) characterize the effect of smoking cessation on sleep using state-of-the-art techniques in measurement of central and autonomic nervous system arousal, in a sample larger than the total number of smokers studied in sleep laboratories to date; 2) determine the impact of currently recommended smoking cessation treatments on sleep and sleep disturbance; 3) evaluate the impact of smoking cessation treatments on daytime sleepiness and mood; and, 4) assess the effect of sleepiness and mood disturbance on relapse. The following hypotheses will be tested: 1) Smoking cessation will be associated with disturbed sleep, increases in EEG and autonomic arousals from sleep, and a relative shift to sympathetico-vagal balance during the sleep period; 2) The use of bupropion and transdermal nicotine will lead to further increases in sleep disturbance over and above those seen with smoking cessation; 3) The cessation-related and treatment-related increases in sleep disturbance will be positively related to an increase in daytime sleepiness and negative mood, and decreased daytime performance; 4) The cessation-related increase in sleep disturbance, daytime sleepiness, and negative mood will positively correlate with relapse within twelve months; 5) The negative impacts of pharmacotherapy treatment for the withdrawal effects of smoking cessation will be greater in women than in men. The results of this project will be particularly important for the development of targeted treatment approaches designed to ameliorate sleep disruption as part of an overall smoking cessation strategy.