This paper reviews findings from placebo-controlled human experimental studies of the effects of nicotine on subjective experience. Studies are grouped according to whether participants were smokers (significantly nicotine deprived, minimally nicotine deprived) or non-smokers. Within each category, studies are also grouped according to method of nicotine administration (e.g., smoked tobacco, nasal spray) and nicotine dose. This review of studies is preceded by a discussion of several methodological issues in studies of nicotine and mood. The principal findings of this review are: (1) there is a linear relationship between nicotine dose and measures of drug high (e.g., head rush, euphoria) in significantly nicotine-deprived smokers; (2) there appear to be few positive or negative main effects of nicotine on mood in minimally nicotine-deprived smokers; (3) nicotine has positive effects (e.g., increases head rush) and negative effects (e.g., increases tension) in non-smokers; (4) stronger effects of nicotine on mood emerge when individual difference variables (e.g., neuroticism) and situational contingencies (e.g., exposure to stressful stimuli) are examined. Additional studies with minimally nicotine-deprived smokers and non-smokers are needed to further specify the conditions under which nicotine affects mood and other subjective experience. The review concludes with a discussion of putative mechanisms that may mediate the interaction between nicotine and moderating variables on affect and with suggestions for future research.