This study examines the genetic influence ofβ-adrenergic receptor gene polymorphisms (β2-AR Arg16Gly andβ3-AR Trp64Arg) on the relationship of birthweight to longitudinal changes of blood pressure (BP) from childhood to adulthood in 224 black and 515 white adults, aged 21–47 years, enrolled in the Bogalusa Heart Study. Blacks showed significantly lower birthweight and frequencies ofβ2-AR Gly16 andβ3-AR Trp64 alleles and higher BP levels and age-related trends than whites. In multivariable regression analyses using race-adjusted BP and birthweight, low birthweight was associated with greater increase in age-related trend of systolic BP (standardized regression coefficientβ=−0.09,P=.002) and diastolic BP (β=−0.07,P=.037) in the combined sample of blacks and whites, adjusting for the first BP measurement in childhood, sex, age, and gestational age. Adjustment for the current body mass index strengthened the birthweight-BP association. Importantly, the strength of the association, measured as regression coefficients, was modulated by the combination ofβ2-AR andβ3-AR genotypes for systolic (P=.042for interaction) and diastolic BP age-related trend (P=.039for interaction), with blacks and whites showing a similar trend in the interaction. These findings indicate that the intrauterine programming of BP regulation later in life depends onβ-AR genotypes.