To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors on renal outcome in patients with renal insufficiency, a 2-part study was conducted. Part A consisted of a retrospective 1-year analysis of 80 hypertensive outpatients with serum creatinine levels of 1.5–6 mg/dl, 39 of whom received ACE inhibitors and other antihypertensive agents and 41 of whom received only other antihypertensive agents. Median serum creatinine levels in the ACE group rose acutely from 2.33 to 2.7 mg/dl after 1 month of therapy and remained stable thereafter. Serum creatinine levels more than doubled in 2 patients. In controls, median serum creatinine levels rose gradually over 12 months from 2.39 to 3.45 mg/dl, and serum creatinine more than doubled in 9 patients. Part B consisted of a prospective follow-up of patients for a second year; 34 patients in the treatment group and 32 controls were then analyzed; median serum creatinine level was 3.0 vs. 4.4 mg/dl after 2 years; 2 of 34 vs. 6 of 32 patients were on dialysis; serum creatinine level had more than doubled in 4 of 34 vs. 8 of 32. These results suggest that ACE inhibitors are more effective than other antihypertensive agents in reducing the progression of renal failure.