The purpose of this revised application is to expand and continue the research begun in the previous funding period, Treatment of Nicotine Dependence in an HMO Setting, in which 1,524 individuals enrolled in a health care system received treatment with bupropion SR and behavioral counseling and were then followed for 12 months after their target quit date to determine smoking status. The results of this study demonstrate that: (1) an effectiveness trial can be conducted in a large health care system; (2) 150 and 300 mg doses of bupropion SR are equally effective for smoking cessation at 12 month follow-up; (3) proactive telephonic based (PTB) treatment is more effective than a tailored mailing (TM) program; (4) female gender, lower education, and higher levels of depression are independent risk factors for post-treatment smoking; and (5) there is substantial heterogeneity in treatment outcome among women and men at one year follow-up. In addition, cost-effectiveness analyses showed that 150 mg bupropion SR is more cost effective than the 300 mg dose from both the payer (i.e., employer) and societal perspectives. The next generation of this research program will evaluate the effectiveness of three different intervention approaches in combination with 150 mg bupropion SR: a proactive telephone-based (PTB) tobacco cessation program, a web-based (WB) tobacco cessation program, and a combined PTB+WB program. Participants (n=1,200) will be randomized to one of the three behavioral treatment conditions, receive an eight week course of 150 mg bupropion SR, and then followed at various points throughout a 12-month period to determine indices of medication adherence, treatment utilization, point-prevalent smoking outcomes and continuous nonsmoking. The specific aims of this project are: (1) To determine the relative effectiveness of each version of the behavioral treatment in combination with 150 mg bupropion SR; (2) To determine group differences in adherence to both the bupropion SR and behavioral conditions; (3) To examine heterogeneity in responsiveness to the three treatment conditions with Classification and Regression Tree (CART) Analysis; (4) To characterize process variables related to recruitment, implementation, barriers to treatment, exposure to intervention, satisfaction with treatment, treatment contamination, and program maintenance; (5) To determine the cost-effectiveness of the different delivery modes offered in the proposed trial; and (6) To disseminate the results of the proposed trial to the adult GHC consumers (approximately 500,000), providers, and other key stakeholders in GHC's integrated care model (n=1,400).