Nonsteroidal antiinflammatory drugs (NSAIDs) are known to attenuate the antihypertensive effects of a variety of antihypertensive agents including diuretics, beta-blockers, and vasodilators. Because of their unique mechanisms of actions, calcium channel blockers may not be subject to this interaction. This multicenter, double-blind, randomized, placebo-controlled study was designed to assess the effect of NSAID therapy on blood pressure control in stable hypertensive patients treated with a calcium channel blocker. One hundred patients with stable blood pressure control on 30 mg nicardipine three times a day were treated with 375 mg naproxen twice a day or placebo for 4 weeks. The mean diastolic blood pressures and estimated mean arterial pressures in both groups changed < 1 mm Hg during the 4 weeks of study drug treatment. None of the changes was significantly different from baseline and the two treatment groups were not significantly different from each other. Body weight in the placebo-treated patients did not change significantly whereas body weight in the naproxen-treated patients increased significantly, from 90.3 +/- 3.2 kg to 91.0 +/- 3.2 kg (mean = 0.7, P = .0003). At 4 weeks there was a mean loss of 0.1 kg in the placebo group and a mean gain of 0.4 kg in the naproxen group compared to baseline weights, neither of which was statistically significant (P = .60 and P = .071, respectively). These results indicate that despite a significant increase in body weight, the antihypertensive action of the calcium channel blocker nicardipine is not significantly affected by cotreatment with naproxen.