Sustained-release bupropion and nortriptyline have been shown to be efficacious in treating cigarette smoking. Psychological intervention is also recognized as efficacious. The cost and cost-effectiveness of the 2 drug therapies have not been estimated. It was hypothesized that nortriptyline would be more cost-effective than bupropion. Hypotheses were not originally proposed concerning the cost-effectiveness of psychological versus drug treatment, but the 2 were compared using exploratory analyses. This was a 3 (bupropion versus nortriptyline versus placebo) by 2 (medical management alone versus medical management plus psychological intervention) randomized trial. Participants were 220 cigarette smokers. Outcome measures were cost and cost-effectiveness computed at week 52. Nortriptyline cost less than bupropion. Nortriptyline was more cost-effective than bupropion; the difference was not statistically significant. Psychological intervention cost less than the 2 drug treatments, and was more cost-effective, but not significantly so. Prospective investigations of the cost and cost-effectiveness of psychological and pharmacological intervention, using adequate sample sizes, are warranted.