Background: Whether individuals who were small at birth are at increased risk of developing cardiovascular disease (the Barker hypothesis) is a topic of great controversy. Although an increased risk has been suggested by several reports, the reports have been criticized for being based on ill-defined populations, for the large numbers of subjects who were unavailable for follow-up, and for inadequate control of socioeconomic status. Objective: To determine whether a woman's weight and gestational age at birth predict the development of hypertension during her subsequent pregnancies. Design: Prospective observational study. Subjects: Women born in Copenhagen, Denmark, as subjects in the Danish Perinatal Study (1959-1961) were traced through the Danish Population Register. Information was obtained on their pregnancies from 1974 to 1989. Main Outcome Measures: Onset of hypertension in pregnancy, defined by the presence of a systolic blood pressure of 140 mm Hg or greater or a diastolic blood pressure of 90 mm Hg or greater on 2 visits at or after 140 days gestation. Results: Hypertension developed in 11.3% of the pregnant women who were small for gestational age at birth, compared with 7.2% of the pregnant women who were not small for gestational age at birth (odds ratio [OR], 1.7, 95% confidence interval [CI], 1.1-2.6), and in 9.4% of the pregnancies in women who were preterm at birth, compared with 7.6% of pregnancies in women who were not preterm at birth (OR, 1.3; 95% CI, 0.8-2.0), After adjustment for adult body mass index, smoking, birth order, and hypertension in the subjects' own mothers, the ORs for small-for-gestational-age women and preterm women to develop hypertension during pregnancy were 1.8 (95% CI, 1.1-2.8) and 1.5 (95% CI, 0.96-2.5), respectively. Conclusion: These results support the Barker hypothesis, while addressing many of the methodological criticisms of previous investigations.