Human twin studies have indicated that genetic factors influence whether people do, or do not, smoke and may also influence amount of tobacco used. Studies in the authors' laboratory have demonstrated that inbred mouse strains differ in sensitivity to many actions of a first challenge dose of nicotine. These strain differences are due, in part, to differences in the number of brain nicotinic receptors. Mouse strains also differ in the development of tolerance to nicotine and subtle differences in chronic nicotine-induced increases in the number of brain nicotinic receptors have been detected. Preliminary data suggest that mouse strains differ in oral self-selection of nicotine containing solutions which may suggest genetic influences on rewarding effects on nicotine. These results suggest that humans may also differ, for genetic reasons, in sensitivity to nicotine, in the development of tolerance to nicotine and in rewarding effects of nicotine. Presumably, those individuals who are resistant to nicotine's toxic actions and sensitive to its rewarding effects are more likely to become smokers if tobacco experimentation is initiated.