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Little is understood about biobehavioral mechanisms that mediate the comorbidity between cigarette smoking and depression. We hypothesized that expectancies about nicotine’s reinforcing effects are associated with vulnerability to depression, and may partially explain the relationship between history of depression and smoking. Young adult smokers and never smokers (N = 175, mean age = 19.9 years, S.D. = 3.2) were assessed for history of depression and expectations about the negative (e.g., dispels bad moods) and positive (e.g., increases pleasure) reinforcing effects of smoking. Results are inconsistent with the premise that negative reinforcement expectancies mediate the comorbidity between depression and nicotine dependence. Instead, findings suggest that young adults with a prior history of major depression hold exaggerated expectations about nicotine’s positive effects, which could enhance their likelihood of initiating smoking.