Twenty-eight patients with mild to moderate essential hypertension well controlled by atenolol entered a five-week, double-blind, placebo-controlled trial of the effects of sulindac and naproxen on blood pressure (BP) control. Atenolol alone was administered during weeks 1, 3, and 5. Naproxen or sulindac was administered with atenolol during week 2, with crossover during week 4. Data were analyzed for 27 of the patients (one dropped out after developing a skin rash). Naproxen significantly increased the systolic BP compared with placebo (mean 4.0 mm Hg; 95 percent confidence interval, 1.1-7.0; p less than 0.05). There were no significant differences in systolic BP during sulindac administration compared with placebo or naproxen. No significant effects on diastolic BP were observed. Weight was increased by naproxen and sulindac compared with placebo (mean 0.6-0.8 kg, p less than 0.05), although not to a clinically significant extent. One-week therapy with naproxen has a greater potential than sulindac to increase systolic BP in well-controlled hypertensive patients receiving atenolol; however, the increase is minor and unlikely to be of clinical significance.