Worldwide experience with captopril and enalapril showed that angiotensin-converting enzyme (ACE) inhibitor monotherapy in hypertensive patients rarely caused renal dysfunction. The ACE inhibitors in combination with potent vasodilating drugs and diuretics may produce sudden systemic normotension or hypotension that may impair glomerular filtration at reduced renal perfusion pressure. Reversible renal insufficiency developed during the 13th week of hydrochlorothiazide-enalapril-alpha methyldopa therapy in patient 1 and during the 6th week of hydrochlorothiazide-enalapril treatment in patient 2. Systemic hypotension in patient 1 and routine biochemical monitoring in patient 2 was the first clue of renal insufficiency. Renal angiography was normal in both patients. Renal insufficiency resolved after stopping all drugs temporarily and did not recur on other antihypertensive drug regimens. These data suggested the importance of systemic arterial blood pressure as the best clinical determinant of renal function in hypertensive patients receiving an ACE inhibitor in combination with other antihypertensive agents.