This study examines the genetic influence of beta-adrenergic receptor gene polymorphisms (beta(2)-AR Arg16Gly and beta(3)-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 of beta(2)-AR Gly16 and beta(3)-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 coefficient beta = -0.09, P = .002) and diastolic BP (beta = -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 of beta(2)-AR and beta(3)-AR genotypes for systolic (P = .042 for interaction) and diastolic BP age-related trend (P = .039 for 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 on beta-AR genotypes.