Objective: To examine the effects of oral and transdermal estrogen replacement therapy (ERT) on ambulatory 24-hour blood pressure (BP) recordings. Methods: In a nonrandomized, prospective study, 90 normotensive, oophorectomized women, ages 30-59 years, underwent ambulatory 24-hour BP measurements at study entry and after 3 and 6 months of either oral (n = 50) or transdermal (n = 40) ERT. Results: In the women receiving transdermal estrogen, we observed a change in mean nighttime systolic BP of -4.2 mmHg (95% confidence interval [CI] -7.7, -0.7; P = .039) after 6 months' treatment. There was a change in mean daytime diastolic BP after 3 months (-3.3 mmHg; 95% CI -5.5, -0.9; P = .016) and 6 months (-4 mmHg; 95% CI -6.8, -1.2; P = .014), and in mean nighttime diastolic BP after 3 months (-3.8 mmHg; 95% CI -6.6, -0.9; P = .027) and 6 months (-4.4 mmHg: 95% CI -7.1, -1.7; P = .005). No significant BP changes were observed in the women taking oral estrogen. Although the statistical power to detect a change of 4 mmHg at the 5% significance level was 90% for diastolic BP, it was weaker for systolic BP (63%) in this group. However, in more than one-third of the women receiving either treatment, a statistically significant increase in BP was observed. Conclusions: Transdermal ERT was associated with a reduction in mean ambulatory BP, whereas oral treatment; did not alter BP. Although the overall effect of estrogen was to lower BP, individual responses were variable, and BP increased in more than one-third of the women on either treatment. Therefore, long-term monitoring of ambulatory measurements may be required. Copyright (C) 1997 by The American College of Obstetricians ann Gynecologists.