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To examine the effectiveness of transdermal selegiline for producing cigarette smoking abstinence. Adult smokers were randomly assigned to receive selegiline transdermal system (STS) or placebo given for 8 weeks. All participants received cognitive behavior therapy (CBT). Follow-ups were conducted at 25 and 52 weeks.Community smoking cessation clinic.243 adult smokers (≥18 years of age; ≥10 cigarettes/day).Expired-air carbon monoxide confirmed 7-day point prevalence abstinence. STS was not superior to placebo. More women than men were abstinent at 52 week follow-up (28% vs 16%, P < 0.05). Behavioral activation (BAS) moderated treatment response (P = 0.01). The survival rate through week 52 for those with high ‘drive’ scores on the BAS was 47% if assigned to selegiline and 34% if assigned to placebo. The survival rate for those with low ‘drive scores’ on the BAS was 35% if assigned to selegiline compared to 53% if assigned to placebo.Transdermal selegiline does not appear generally effective in aiding smoking cessation though there may be a selective effect in those smokers with low ‘behavioral activation’.