The brain mechanisms underlying the cause of nicotine dependence are unknown, however, hostility traits are associated with increased susceptibility to nicotine dependence. We used FDG PET to measure brain metabolic response to nicotine administered by patch while the subject performed the Bushman aggression task in 86 high- and low-hostility subjects. Low-hostility trait subjects demonstrated no significant change in brain metabolic response to nicotine. In marked contrast, high-hostility non-smokers subjects demonstrated dramatic metabolic changes to low dose (3.5 mg patch) as did high-hostility smokers to high dose nicotine (21 mg patch) throughout the brain bilaterally (p<0.025). Correlational analyses demonstrated greater metabolic changes in response to nicotine in subjects with greatest hostility trait measures. The observed differences were not a consequence of plasma nicotine or cotinine levels. These metabolic changes were not observed when subjects performed a sustained attentional task (continuous performance task; CPT). Behaviorally, high-hostility subjects had higher ratings of anger, impatience, irritability and nervousness, and lower ratings of happiness, relaxation and curiosity than low-hostility subjects. Smokers had significantly greater scores on impatience and restlessness than non-smokers. This PET study demonstrates a conspicuous lack of the brain metabolic response to nicotine in low-hostility non-smokers in contrast to a dramatic brain response to nicotine in high hostility subjects. This biological difference in brain metabolic response to nicotine between high and low hostility trait subjects may explain differences in susceptibility to nicotine dependence.