This study determined the effect of nonsteroidal anti-inflammatory drug (NSAID) administration on blood pressure in hypertensive patients taking hydrochlorothiazide (HCTZ). Ninety-seven patients with mild essential hypertension and a musculoskeletal indication for NSAID use were studied in a three-phase, multi-center, double-blind, randomized, parallel study based in 15 academic and community clinics. Patients served as their own controls. Patients with stable hypertension, not taking antihypertensive or NSAID medications, were treated with HCTZ 50 mg/day. After 4 to 5 weeks of treatment and documented stable blood pressure, naproxen 375 mg twice a day or ibuprofen 800 mg three times a day was added. Blood pressure was measured at 2 and 4 weeks of NSAID therapy. The average diastolic blood pressure was 97.5 +/- 2.4 mm Hg and the average of the mean arterial pressure (MAP) was 116.8 +/- 6.04 before treatment with HCTZ. Hydrochlorothiazide treatment decreased diastolic blood pressure to 83.1 +/- 5.6 mm Hg, and MAP to 101.1 +/- 6.5 mm Hg. With naproxen or ibuprofen treatments, mean diastolic blood pressure increased less than 3 mm Hg. At 2 weeks, ibuprofen increased diastolic blood pressure by 2.6 mm Hg (P = .004) and naproxen increased diastolic blood pressure 0.7 mm Hg (P = .40). Both ibuprofen and naproxen significantly increased diastolic pressure at 4 weeks (2.1 mm Hg, P = .042; and 1.8 mm Hg, P = .043, respectively). There was no correlation between the pre-NSAID blood pressure and the magnitude of change after 2 or 4 weeks of treatment. Changes in MAP reflected a pattern similar to diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)