Maternal cigarette smoking is a risk factor for adolescent smoking. One possible explanation for increased smoking by human adolescents after maternal nicotine exposure is that exposure increases nicotine preference. However, it is difficult to separate the biological and social causes of smoking behavior in humans. This experiment examined the relationship between maternal nicotine exposure and nicotine preference in periadolescent offspring using a mouse model of oral nicotine consumption. Pregnant females were provided saccharin-flavored water containing 50 microg/ml nicotine (n = 4) or no nicotine (n = 5) from the ninth day of gestation through weaning on postnatal day (PD) 21. Offspring from these females were tested for nicotine preference during periadolescence (PDs 35-42) by providing access to both saccharin-only and nicotine solutions (50 microg/ml) 24 hr a day in the home cage in a two-bottle choice test. Male mice exposed maternally to nicotine (n = 9) exhibited an increased nicotine preference in adolescence compared to non-nicotine exposed controls (n = 12). Maternal nicotine exposure did not alter nicotine preference by periadolescent female mice. Nicotine consumption was confirmed by serum cotinine measurement. These data are consistent with human epidemiological reports that maternal nicotine exposure is associated with increased risk of cigarette smoking. Differential outcomes for males and females suggest that different processes underlie sex differences in nicotine consumption following maternal nicotine exposure.