Most smokers attempting to quit will relapse, even when using evidence-based cessation treatment. This illustrates the need for better understanding of the relapse process to thereby improve cessation treatments. Although the impact of stress sensitivity on relapse is clear, little research has precisely examined stress reactivity in addicted individuals. Further, most research on relapse focuses on affect surrounding self-administration, and does not address potentially important preconsumption processes such as anticipation of use. We examined the effects of anticipation and actual smoking on stress reactivity in 34 deprived smokers withdrawn for 24 hr and 37 nondeprived smokers, with 37 nonsmoker controls. Using a cued shock stressor task, we measured stress reactivity via startle potentiation and self-reported anxiety. After completing the task once, smokers anticipated smoking a cigarette resting in front of them while they completed the task a second time. Smokers then smoked before completing the task a third and final time. Nonsmokers anticipated and drank water as a control. Anticipation of smoking significantly attenuated both startle potentiation and self-reported anxiety to shock cues for deprived smokers relative to nondeprived smokers. Smokers' stress reactivity was not reduced by smoking beyond the prior effect of anticipation. These results suggest that anticipation, rather than actual drug consumption, may drive the primary reinforcing effect of reduced stress reactivity in smoking. Future research is needed to understand this effect of anticipation on drug use and to determine whether anticipation would make an effective intervention target for addiction and other psychopathology that exhibits increased stress sensitivity.