The primary purpose of this project is to examine basic neurobiological and cognitive processes related to smoking relapse. There are two premises underlying the proposed studies. First, exposure to smoking cues can elicit a set of neurobiological and cognitive responses that systematically increases the likelihood that one will smoke. Second, attempts to regulate such cue-elicited affective responses in abstinent-seeking subjects will typically recruit executive control processes mediated by dorsolateral prefrontal cortex. Thus, smokers with low levels of working memory will be more vulnerable to these effects, because they are less able to execute coping responses to forestall relapse than smokers with high working memory capacity. The proposed laboratory functional magnetic resonance imaging (fMRI) studies will merge the research approaches and theoretical perspectives of human neuroscience, cognitive psychology, and drug cue reactivity to examine the effects of treatment-seeking status, perceived opportunity to smoke, and alternative coping techniques on the regulation of smoking cue reactivity. Active smokers and smokers interested in participating in a smoking cessation program will be exposed to smoking or control cues, while deprived of nicotine. Study 1 (n=100) will test whether cue exposure activates regions of the prefrontal cortex supporting cognitive control processes. Study 2 (n = 50) will investigate the impact of coping with smoking cues across cognitive, behavioral, and neurobiological response domains, and link changes in working memory to levels of activation in the dorsolateral prefrontal cortex. Study 3 (n= 100) will test the effects of working memory capacity (high vs. low) and specific coping technique (high self-relevance vs. low self-relevance) on cognitive and neurobiological responding. This model-driven experimental research will examine neurobiological and cognitive mechanisms that may link cue-elicited craving to relapse. By integrating fMRI methods with measures derived from basic psychology, this interdisciplinary project aims to advance knowledge of neurobiological and cognitive processes in addiction. Regardless of the outcome, the studies will provide critical data regarding observable effects of cue-elicited craving on smokers, which will improve understanding of factors contributing to the etiology, maintenance, and treatment of nicotine addiction.