Background/Aims: Cigarette craving is a core symptom of smoking withdrawal, which is more intense and more frequently observed in smokers with depressed mood. Using self-reports and electroencephalographic (EEG) indices of frontal hemispheric asymmetry, which has been shown to be sensitive to mood states, the purpose of this study was to investigate the neural basis of cue-elicited cigarette craving, its variation with experimentally induced depressed mood, and with differences in gender and smoker type. Methods: Cigarette-cue reactivity was examined in 11 (5 male) regular and 11 (6 male) light smokers in two sessions involving the induction of neutral or depressed mood. Results: Frontal EEG alpha asymmetry changes reflecting left frontal hypoactivation were evident with cigarette-cue exposure, particularly in female smokers. During cigarette-cue exposure, EEG evidenced both decreases and increases in brain state activation, with the latter activational increments also being influenced by depressed mood. Exposure to the cigarette cue, in addition to increasing withdrawal symptoms, increased cravings and negative affect, these latter effects being more evident in female and regular smokers. Conclusion: These findings, which appear to provide a physiological basis for ‘withdrawal-like’ negative affective experiences during craving, are discussed in relation to theories of drug reinforcement and smoking motivation.