Objective: Expectancies about nicotine's ability to alleviate negative mood states may play a role in the relationship between smoking and depression. The authors examined the role of negative affect regulation expectancies as a potential mediator of depression (history of depression and depressive symptoms) and smoking among college students. Participants and Methods: As part of a larger study, 315 undergraduate smokers completed a 296-item survey from January to May of 2001 and 2002. Results: Cross-sectional analyses revealed that negative affect regulation expectancies fully mediated the positive relationship between depressive symptoms and level of smoking. Conclusions: Although depressive symptoms are associated with higher levels of tobacco smoking, the expectation that smoking will reduce negative emotions is 1 factor that accounts for this relationship. (Contains 1 table and 1 figure.)