E-cigarettes are quickly becoming the most commonly used inhaled tobacco product in the U.S. after tobacco cigarettes. Although e-cigarettes may pose a threat to the public health, more research on these products is needed to inform and guide FDA regulation. Indeed, no data exist on the time course or clinical significance of e-cigarette withdrawal, and therefore a complete understanding of the addictive nature of these products is unknown. As the first of any empirical study to focus on e-cigarette withdrawal effects, the objectives of the proposed project are to: 1) characterize the early time course of e-cigarette withdrawal effects; 2) evaluate the clinical significance of early e-cigarett withdrawal effects; 3) compare the time course and clinical significance of early e-cigarette withdrawal effects to the time course and clinical significance of early tobacco withdrawal effects; and 4) examine moderators of the time course and clinical significance of early e-cigarette withdrawal effects. Participants will be 150 e-cigarette users and 150 tobacco cigarette users who will participate in two counterbalanced experimental sessions involving either 4 hours of abstinence or smoking as usual. Withdrawal measures will include negative affect (Wisconsin Smoking Withdrawal Scale), physical symptoms (Minnesota Nicotine Withdrawal Scale), multifaceted craving (Tobacco Craving Questionnaire), anhedonia (Tripartite Pleasure Inventory), perceived reinforcement value of smoking (Cigarette Choice Procedure), and open-ended report. After baseline assessment, withdrawal measures will be administered every 30 minutes. At the conclusion of the 4-hour period, participants will complete the Behavioral Smoking Lapse Analogue Task, a clinically relevant analogue task of smoking lapse that measures the ability to resist the temptation to smoke under conditions in which it is advantageous to remain abstinent. Candidate moderator variables assessed at intake will include demographic characteristics, e-cigarette history and use characteristics, smoking dependence, thoughts about abstinence, abstinence-related expectancies, and intolerance for smoking abstinence discomfort. Analyses will evaluate e-cigarette withdrawal effect differences between abstinent and non-abstinent experimental sessions, test the relationships between e-cigarette withdrawal effects and performance on the Behavioral Smoking Lapse Analogue Task, determine if withdrawal effects and their relationships to performance on the Behavioral Smoking Lapse Analogue Task differ between e-cigarette users and tobacco cigarette users, and evaluate whether e-cigarette withdrawal effects and their relationships to performance on the Behavioral Smoking Lapse Analogue Task differ across levels of the candidate moderator variables. In conclusion, the proposed study will facilitate FDA regulation of e-cigarettes by informing the addictive nature of these products and determining those populations that may be especially vulnerable to e- cigarette addiction.