Objective: To explore the sex-specific benefits and risks of treatment of stage 1 diastolic hypertension. Methods: Participants were African-American and white hypertensive men (n=557) and women (n=345) (age range, 45 to 69 years) with a diastolic blood pressure less than 100 mm Hg. Participants were randomized to treatment with placebo, chlorthalidone (15 mg/d), acebutolol hydrochloride (400 mg/d), doxazosin mesylate (2 mg/d), amlodipine besylate (5 mg/d), or enalapril maleate (5 mg/d); all were given nutritional-hygienic intervention. Results: After 4 years, women who were randomized to lifestyle intervention only were less likely to be receiving step 1 therapy alone (placebo) than men who were randomized to placebo therapy (46% vs 66%, respectively, P<.01). There were significantly greater decreases in the mean systolic blood pressure in both men and women who were assigned to treatment with active drugs compared with those participants who were receiving placebo therapy; differences among treatments with active drugs were similar between men and women. Men experienced larger falls in their total and low-density lipoprotein cholesterol and triglyceride levels regardless of the treatment assignment than did women; however, there were no significant sex-by- treatment interactions. Quality-of-life indexes were generally improved with active drug treatment compared with placebo therapy in both sexes; there was a sex-by-treatment interaction for the general health index. The relative risk (RR) for combined clinical events was similar in women (RR, 0.64; 95% confidence interval [CI], 0.36 to 1.16) and in men (RR, 0.67;95% CI, 0.40 to 1.14) who were assigned to treatment with all active drugs combined, compared with those who were receiving placebo therapy. Conclusion: In these exploratory analyses, men and women who were assigned to treatment with active drugs experienced greater and generally similar benefits from treatment than those participants who were assigned to lifestyle intervention only.