Although overall rates of cigarette smoking have declined over the past 40 years, the use of spit tobacco (ST) has tripled. The use of ST can lead to nicotine addiction and physical dependence. ST use is known to increase the risk of periodontal disease and oral cancer. Moreover, ST use increases the risk for cancer of the esophagus, larynx, stomach and pancreas and the risk of cardiovascular disease. Effective interventions are needed to assist ST users to stop. Bupropion, a monocyclic anti- depressant that inhibits the neuronal re-uptake of norepinephrine and dopamine and may also selectively inhibit neuronal nicotinic receptors, has demonstrated efficacy for smoking cessation. In a placebo-controlled pilot study, we have shown possible treatment effects of sustained release bupropion (SR) in ST user. Our aims are: 1) To evaluate the efficacy of a 12-week course of bupropion SR rates of abstinence from all tobacco use; 2) To evaluate the efficacy of a 12-week course of bupropion SR compared to placebo on the end of treatment and 12- month rates of abstinence from all tobacco use; 2) To evaluate the efficacy of a 12-week course of bupropion SR compare to placebo on the end of treatment and 12-month rates of abstinence from ST; 3) To determine what baseline characteristics in addition to medication assignment are associated with abstinence from all tobacco and from ST, at the end of treatment and at 12 months; 4) To determine the association between baseline urine tobacco alkaloids with self-reported tobacco use behavior and level of nicotine dependence assessed using the Fagerstrom Tolerance Questionnaire modified for ST users; 6) To determine if ST users successful in abstaining from ST switch to a nicotine-replacement product or a different tobacco product (cigarettes, pipe, or cigars). In a randomized, double-blind, placebo-controlled trial, we will compare bupropion SR to placebo in 320 regular users of ST. Active or placebo bupropion will be taken for a total of 12 consecutive weeks starting one week before the target quit date. Behavioral intervention will be provided for all subjects.