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Few studies have reported interactions between maternal smoking and other maternal characteristics and exposures. We examined maternal smoking in a cohort study for which data from 3 generations were available to examine maternal characteristics and exposures from a life-course perspective.We had data from 3 generations: women enrolled in the U.S. Collaborative Perinatal Project (CPP) between 1959 and 1965 at the Baltimore site (G1); daughters (G2) of those G1 mothers who were followed to ages 27–33 years in the Pathways to Adulthood study; and children (G3) born to the G2 women who provided pregnancy and birth information during the Pathways study. These data allowed examination of exposures that occurred to the mother during her childhood and in utero.We found evidence of a 3-way interaction effect on birth weight for maternal smoking in pregnancy, maternal exposure to smoking in utero (grandmaternal smoking), and maternal parity. Maternal smoking reduced birth weight in 3 of the subgroups, with the size of the effect on birth weight moderated by parity and the mother's own in utero exposure to smoking.A mother's prenatal exposure to smoke may affect the birth weight of her offspring. This effect would be consistent with both the accumulation-of-risk and the fetal-programming hypotheses.