RATIONALE:Policies that establish a standard for reduced nicotine content in cigarettes can decrease the prevalence of smoking in the USA. Cigarettes with nicotine yields as low as 0.05 mg produce substantial occupancy of nicotinic acetylcholine receptors (26%), but women and men respond differently to these cigarettes. OBJECTIVE:This study aimed to measure responses to smoking cigarettes that varied widely in nicotine yields, investigating whether sex differences in the effects on craving, withdrawal, and affect would be observed at even lower nicotine yields than previously studied, and in young smokers. METHODS:Overnight abstinent young smokers (23 men, 23 women, mean age 22.18) provided self-reports of craving, withdrawal, and affect before and after smoking cigarettes with yields of 0.027, 0.110, 0.231, or 0.763 mg nicotine, and evaluated characteristics of each cigarette. RESULTS:Compared to abstinent young men, abstinent young women reported greater negative affect, psychological withdrawal, and sedation, all of which were relieved equally by all cigarettes. Men but not women reported greater craving reduction, perceived nicotine content, and cigarette liking with increasing nicotine dose. CONCLUSIONS:Men may experience less smoking-related relief of craving, and enjoy cigarettes less, if nicotine yields are reduced to very low levels. Conversely, women respond equally well to cigarettes with nicotine yields as low as 0.027 mg as to cigarettes with nicotine yields 28-fold higher (0.763 mg). These differences are relevant for policy regarding reduced nicotine in cigarettes and may influence the efficacy and acceptability of reduced-nicotine cigarettes as smoking cessation aids.