The present study evaluated whether anxiety sensitivity (AS) was related to negative reinforcement smoking motives and increased risk of relapse during the early stages of a quit attempt. Specifically, the role of AS was evaluated in 60 smokers with past major depressive disorder (MDD) during smoking cessation. Consistent with expectations, AS scores, as indexed by the 16-item Anxiety Sensitivity Index (ASI) [Behaviour Research and Therapy 24 (1986) 1], were positively correlated with smoking to reduce negative affect but were not significantly correlated with smoking for other reasons. Higher ASI scores also were associated with increased risk of lapsing during the first 7 days after quit day. Results suggest that smokers with heightened levels of AS may smoke more often to manage negative moods and may be less able to tolerate early withdrawal symptoms, specifically during early stages of a quit attempt.