Background - Low birth weight may be associated with high blood pressure in later life through genetic factors, an association that may be explained by alterations in sympathetic and parasympathetic activity. We examined the association of birth weight with cardiac pre-ejection period and respiratory sinus arrhythmia (indicators of cardiac sympathetic and parasympathetic activity, respectively) and with blood pressure in 53 dizygotic and 61 monozygotic adolescent twin pairs. Methods and Results - Birth weight of the twins was obtained from the mothers. Pre-ejection period and respiratory sinus arrhythmia were measured with electrocardiography and impedance cardiography at rest, during a reaction time task, and during a mental arithmetic task. In the overall sample, lower birth weight was significantly associated with shorter pre-ejection period at rest, during the reaction time task, and during the mental arithmetic task (P=0.0001, P<0.0001, and P=0.0001, respectively) and with larger pre-ejection period reactivity to the stress tasks (P=0.02 and P=0.06, respectively). In within-pair analyses, differences in birth weight were associated with differences in pre-ejection period at rest and during both stress tasks in dizygotic twin pairs (P=0.01, P=0.06, and P=0.2, respectively) but not in monozygotic twin pairs (P=0.9, P=1.0, and P=0.5, respectively). Shorter pre-ejection period explained approximately 63% to 84% of the birth weight and blood pressure relation. Conclusions - Low birth weight is associated with increased sympathetic activity, and this explains a large part of the association between birth weight and blood pressure. In addition, our findings suggest that the association between birth weight and sympathetic activity depends on genetic factors.