Epidemiological studies have consistently shown an inverse association between birth weight and systolic blood pressure in later life after adjustment for current size. To examine whether this association is explained by intrauterine or genetic factors, we investigated birth weight and blood pressure data in 53 dizygotic and 61 monozygotic adolescent twin pairs. Birth weight was obtained from the mothers. Blood pressure measurements were performed 6 times at rest and during mental stress. The dizygotic but not the monozygotic twins with the lowest birth weight from each pair had a systolic blood pressure measured at rest and during the reaction time experiment that was higher compared with their cotwins with the highest birth weight (dizygotic twins: blood pressure at rest, 119. 4+/-9.7 mm Hg versus 117.3+/-8.5 mm Hg, P=0.07, and during a reaction time task, 126.2+/-10.8 versus 123.6+/-9.5, P=0.09; monozygotic twins: blood pressure at rest, 117.4+/-6.4 versus 118. 4+/-9.0, P=0.4, and during a reaction time task, 122.9+/-8.4 versus 124.2+/-10.8, P=0.2). The differences in blood pressure between the cotwins with the lowest and the cotwins with the highest birth weight were different in dizygotic compared with monozygotic twin pairs (for blood pressure at rest, P=0.05; for blood pressure during reaction time, P=0.03). After adjustment for differences in current weight, intrapair differences in birth weight were negatively and significantly associated with differences in systolic blood pressure at rest and during the reaction time task in dizygotic twins (regression coefficient, -5.7 mm Hg/kg [95% confidence interval, -10.4 to -1.0] and -6.3 [-12.7 to 0], respectively) but not in monozygotic twins (-0.1 [-5.4 to 5.2] and +3.5 [-1.8 to 8.8], respectively). Interaction analysis indicated that the associations were different between dizygotic twins and monozygotic twins (P=0.1 and P<0.05, respectively). These data suggest that genetic factors may play an important role in the association between birth weight and blood pressure.