Different theories have been proposed to explain the development of nicotine dependence. Some theories suggest that nicotine has direct reinforcing properties, either positive or negative. That is, nicotine is self-administered because it produces pleasure or positive affect or because it alleviates aversive symptoms associated with withdrawal and/or other nondrug aversive states (e.g., depression). Another possibility is that nicotine has indirect reinforcing properties; that is, nicotine can act as an enhancer of other reinforcers and, as such, it can affect responsivity to reward. This possibility was investigated in the present research. Specifically, it was hypothesised that reward responsivity would decrease in withdrawal; the difference between responsivity in withdrawal and satiation (smoking status) would increase with higher levels of dependency. The effects of smoking status and dependence on affect were also examined. Five experiments tested these hypotheses using a behavioural and a subjective measure of reward responsivity and a subjective measure of affect. There was no evidence for an effect of status on reward responsivity. The behavioural data indicated that withdrawal impacted task performance independently of responsivity to task-contingent reward. Some aspects of pleasure/reward (measured subjectively) were reduced, however, in high dependence smokers. In addition, withdrawn smokers showed reduced positive affect, and high dependence smokers showed increased negative affect, providing support for nicotine’s direct reinforcing properties. Strong support for the indirect reinforcing properties of nicotine, measured behaviourally and subjectively, in humans was not found.