BACKGROUND: Little is known about the contribution of maternal and paternal factors to the inverse association between birth weight and later blood pressure in human offspring. A study of within- and between-family associations of birth weight with blood pressure, which collected data on both parents, would address this gap in our knowledge. METHODS AND RESULTS: The study examined families composed of mother, father, and 2 full sibs delivered between 38 and 41 weeks' gestation within 36 months of each other. A total of 1967 families meeting our inclusion criteria were contacted and 602 were examined (children 5 to 14 years old, 1998 to 2000). Birth weight and gestational age were available from obstetric records. Systolic blood pressure in childhood was inversely associated with birth weight within families (-2.3 mm Hg/kg, 95% CI -4.4 to -0.3) after adjustment for gestational age, sex, height, and weight at examination. The between-family effect (-1.5 mm Hg/kg, -3.1 to 0.0) was strengthened on adjustment for maternal and paternal height and weight, whereas adjustment for paternal and maternal systolic blood pressure at examination independently attenuated the effect. CONCLUSIONS: The existence of an inverse association of birth weight with systolic blood pressure within families (adjusted for height and weight at examination) demonstrates that factors that vary between pregnancies in the same woman (including fetal genotype) can influence the later blood pressure of offspring. We conclude that this apparent fetal programming effect on blood pressure will not be eliminated solely by interventions aimed at modifying growth and cumulative nutritional status from conception through childhood or other fixed characteristics of future mothers.