The renal effects of long-term antihypertensive treatment with enalapril were evaluated in 34 subjects (age, 53 yr; range, 27 to 65) with mild, uncomplicated hypertension. After receiving placebo for 4 wk, subjects were randomly assigned to groups receiving incremental doses of enalapril (10, 20, or 40 mg/day for 4 wk each) in a single morning dose or two divided doses, or of placebo. One subject who received enalapril developed acute renal failure by the end of the study. There was no evidence of glomerular or tubular damage in the other subjects; as measured by 24-hr urinary protein excretion, urinary activity of N-acetyl-β-d-glucosaminidase, and uric acid clearance. During treatment with enalapril, renal plasma flow (measured with 131I-iodohippurate sodium) and glomerular filtration rate increased by 12.1 % and 6.8%. Changes in renal plasma flow correlated inversely with age and final mean arterial pressure and correlated positively with initial plasma renin activity of subjects. Except for an occasional idiosyncratic adverse reaction, enalapril is a safe and effective antihypertensive drug with the unique ability to increase renal function despite a fall in renal perfusion pressure.