Recent years have seen the emergence of research applying functional neuroimaging to the study of cue-elicited drug craving. This research has begun to identify a distributed system of brain activity during drug craving. Functional magnetic resonance imaging (fMRI) was used to examine the effects of smoking expectancy on the neural response to neutral (e.g., roll of tape) and smoking-related (holding a cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hours. As predicted, several brain regions exhibited differential activation during cigarette versus neutral cue exposure. Moreover, instructions about smoking opportunity affected cue-elicited activation in several regions. These results highlight the importance of perceived drug availability in the neurobiological response to drug cues