Few studies have considered the etiological role of the fetal environment on the offspring's substance use. This prospective study examines the relations between the mother's prenatal and current smoking and the offspring's smoking experimentation. A low SES birth cohort of 589 10-year-olds, who have been followed since their gestation, completed a self-report questionnaire about their substance use. Half were female, and 52% were African-American. Detailed data on exposure to tobacco and other substances in the prenatal and postnatal periods were collected from the mothers. During pregnancy, 52.6% of the mothers were smokers; 59.7% were smokers when their children were 10. Six per cent of the children (37/589) reported ever smoking cigarettes, 3% had had one full alcoholic drink, and none had started to use other drugs. Maternal smoking during pregnancy was significantly associated with an increased risk of the child's tobacco experimentation. Offspring exposed to more than 1/2 pack per day during gestation had a 5.5-fold increased risk for early experimentation. Structural equation modeling showed that prenatal tobacco exposure had a direct and significant effect on the child's smoking and that maternal current smoking was not significant. Prenatal tobacco exposure also predicted child anxiety/depression and externalizing behaviors, and these outcomes affected child smoking through the mediating effect of peer tobacco use.