Certain nonsteroidal anti-inflammatory drugs antagonize the action of antihypertensive therapy. Indomethacin has been shown to abrogate the antihypertensive effect of beta-adrenergic receptor blockers, diuretics, converting enzyme inhibitors, and several antihypertensive drug combinations, and the accumulated evidence on piroxicam indicates that it also raises arterial pressure in treated patients. In contrast, sulindac and aspirin do not reverse the effects of antihypertensive drugs, and currently available data indicate that they are the safest cyclooxygenase inhibitors for use in hypertensive patients. In the absence of definitive information on the array of other nonsteroidal anti-inflammatory drugs, they should be considered to pose a risk similar to indomethacin until proved otherwise. The magnitude of the elevation in blood pressure varies between patients, ranging from no effect to dangerous hypertensive responses. Generalized inhibition of the cyclooxygenase enzyme has opposing effects on arterial pressure, lowering renin on one hand and causing sodium retention on the other. Some evidence suggests that cyclooxygenase inhibition causes the greater increments in pressure in patients who initially have low plasma renin activity (often the elderly). The potential for cerebral vascular catastrophes attends these drug interactions in which platelet function also is suppressed by cyclooxygenase inhibition.