There remains controversy over the effects of angiotensin-converting enzyme inhibitors on renal function in patients with heart failure. Accordingly, we investigated the effects of long-term captopril therapy on renal function in 14 patients with congestive heart failure in a double-blind fashion. Creatinine clearance declined (from 61 +/- 21 to 56 +/- 21 ml/min; p less than 0.01), and both serum urea and creatinine rose. Glomerular filtration rate estimated radioisotopically also fell (from 53 +/- 19 to 48 +/- 18 ml/min), although this was not statistically significant. Effective renal plasma flow estimated radioisotopically increased (from 241 +/- 72 to 287 +/- 100 ml/min; p less than 0.05). Thus, filtration fraction--the ratio of glomerular filtration rate to effective renal plasma flow--fell. Because blood pressure also fell, the rise in renal plasma flow indicates a fall in calculated renal vascular resistance. Whole body sodium and chlorine, measured by total body in vivo neutron activation analysis, were unchanged, indicating no long-term natriuresis, despite evidence of clinical improvement. While converting enzyme inhibition causes symptomatic improvement in cardiac failure, there is a concomitant loss of compensatory direct effects of angiotensin II within the kidney, and hence usually some decline in renal function.