It has been suggested that angiotensin-converting enzyme (ACE) inhibitors may also act through the renal prostaglandin (PG) system; moreover, it has been shown that nonsteroidal antiinflammatory drugs (NSAIDs) are capable of reducing the antihypertensive activity of ACE inhibitors. Sixteen essential hypertensive patients (WHO stages, I-II, eight on a low-sodium diet and eight on a high-sodium diet) were treated with enalapril, 20 mg/day per os, for 4 days. On days 3 and 4, ibuprofen, 1,200 mg/day per os, was also given. Enalapril reduced blood pressure, particularly in the group on the low-sodium diet. Urinary 6-keto-PGF1 alpha, an indicator of renal PGI2 production (determined by HPLC-RIA), increased in the first few hours after enalapril in the low-sodium group. Ibuprofen did not reduce the antihypertensive effect of enalapril, nor did it affect plasma renin activity or plasma aldosterone. Only a slight reduction in 6-keto-PGF1 alpha excretion was observed after enalapril plus ibuprofen. It is suggested that the effect of enalapril on urinary 6-keto-PGF1 alpha excretion is largely dependent on factors such as sodium intake.