The long-term (1.5 years) effects of angiotensin-converting enzyme inhibition were evaluated in 22 mostly normotensive patients with nondiabetic renal disease and moderate to severe proteinuria. The nephrotic-range proteinuria of 7.5 g/24 hr fell to 2.9 g/24 hr (-62%) after 2 months' treatment with an angiotensin-converting enzyme inhibitor and remained relatively stable at this level during continued treatment. The antiproteinuric response varied between study days and between individuals. Of note was the fact that the best antiproteinuric response was observed on those study days when no more than the instituted daily sodium intake (50 to 100 mEq/24 hr) was excreted. The sustained reduction in urinary protein excretion was accompanied by an increase in serum albumin and a slight but significant decrease in serum cholesterol. Those patients with the most pronounced initial antiproteinuric response showed less deterioration of renal function, estimated from the slope of the inverse serum creatinine value in time. These data suggest that long-term angiotensin-converting enzyme inhibitor treatment may be beneficial in normotensive patients with nephrotic-range proteinuria, not only to reduce the symptoms of a nephrotic syndrome, but also to prevent further renal damage.