? In this R21 grant application, we propose to conduct a pilot feasibility study to prepare for a future randomized controlled trial testing the efficacy of the antidepressant bupropion for smoking cessation in postpartum women. Maternal smoking increases the risk of infant morbidity and mortality from many causes, including sudden infant death syndrome, respiratory infections, otitis media, and asthma. Reducing smoking in pregnant and postpartum women is a national health objective for 2010. The state-of-the-art smoking cessation treatment for this population, behavioral counseling, has modest success especially in heavy smokers. Adding pharmacotherapy, a standard component of smoking cessation programs in nonpregnant adults, might improve smoking cessation rates in the peripartum setting, but its use has been limited by concern about harming a fetus or breastfed infant. Sustained-release (SR) bupropion is effective for smoking cessation in nonpregnant adults and offers other potential benefits to postpartum women (e.g., mood stabilization and weight management). New data show that a minimal amount of the drug is secreted in human breast milk, providing a compelling rationale for testing bupropion in breastfeeding postpartum smokers. This pilot project will assess the feasibility of a future full-scale trial by: (1) refining recruitment, retention, intervention, and assessment protocols; (2) estimating achievable enrollment and retention rates; and (3) estimating the effect size (difference in smoking cessation rates between drug and placebo groups) in order to plan the sample size for a fully-powered trial. To achieve these aims, we will conduct a pilot randomized double-blind placebo-controlled clinical trial to compare the short-term efficacy of 8 weeks of bupropion SR 150-300 mg/day vs. placebo in 40 postpartum lactating women who smoked equal to or >5 cigarettes per day in the last week of pregnancy. Subjects will be recruited during their post-delivery hospitalization in order to take advantage of the teachable moment of an infant's birth. All subjects will receive """"""""best practice' behavioral smoking cessation counseling. Outcomes, assessed at 2, 4, 8 and 12 weeks postpartum, will include smoking cessation (7-day point-prevalence tobacco abstinence validated by saliva cotinine), depression symptoms, and the tolerability of bupropion in the mother (e.g., medication adherence, adverse effects) and infant (weight gain and maternal report of infant sleep, irritability, and feeding). A substudy will assess breastfed infants' exposure to bupropion. If this pilot is successful, we plan to test the safety and efficacy of bupropion SR in a future full-scale randomized double-blind placebo-controlled trial for smoking cessation in postpartum women. ? ?