Previous studies of smoking on dopamine release in humans were investigated only in smokers. Using nicotine gum, we examined the effect of nicotine on dopamine release in smokers and non-smokers and its relation to the degree of nicotine dependence. Smokers and non-smokers participated in a double-blind, randomized, placebo-controlled cross-over study. They participated in two PET measurements with [11C]raclopride, in which they received either nicotine or placebo. Changes in [11C]raclopride non-displaceable binding potential (BPND) following nicotine administration were quantified. Smokers showed significant decrease in BP in the striatum following nicotine administration, but non-smokers did not show such a decrease. The BPND difference between the two scanning sessions was correlated with the degree of nicotine dependence. The BPND difference might reflect enhanced dopamine release in smokers and the reinforced effect of nicotine. These data suggest the feasibility of our gum method as well as the importance of the degree of dependence in future studies of the nicotine effect on the dopamine system.