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OBJECTIVE: The authors’ goal was to investigate whether maternal smoking during pregnancy is associated with an increased risk of nicotine dependence among adult offspring. METHOD: Prospective data from two samples of offspring in the National Collaborative Perinatal Project, a long-term prospective investigation from pregnancy through adulthood, were combined (N=1,248). Maternal smoking during pregnancy was assessed during each prenatal visit. Offspring smoking behavior and lifetime risk of nicotine dependence were obtained by structured interview with the Diagnostic Interview Schedule; the mean age of the offspring at the time of interview was 29 years. RESULTS: Offspring whose mothers reported smoking a pack or more of cigarettes during their pregnancy were significantly more likely to meet DSM criteria for lifetime tobacco dependence than offspring of mothers who reported that they never smoked during pregnancy. The odds of progressing from smoking to nicotine dependence were almost twice as great for offspring whose mothers smoked heavily during pregnancy. These significant differences remained after adjustments for participants’ gender and age and maternal socioeconomic status and age at pregnancy. Results were comparable for men and women. The findings were specific for tobacco dependence; odds of marijuana dependence were not significantly elevated among the offspring of tobacco smokers. CONCLUSIONS: Offspring of mothers who smoked a pack or more of cigarettes during pregnancy are at elevated risk of developing nicotine dependence but not marijuana dependence as adults. Maternal smoking during pregnancy is a risk factor for subsequent nicotine dependence among offspring.