To assess the effect of furosemide and captopril on renal function and hyponatremia in patients with severe heart failure, we studied two groups of patients with hyponatremia who were receiving digoxin therapy and whose sodium intake was 40 meq/d. One group received captopril and furosemide, the second received captopril. The first group responded to combination therapy with a brisk natriuresis and diuresis, weight reduction, and an increase in serum sodium concentration. Patients who received captopril alone did not respond, despite a similar increase in renal plasma flow and glomerular filtration rate. When furosemide was then administered to patients who had received captopril alone, a brisk natriuresis, weight loss, and correction of hyponatremia followed. Treatment with furosemide is necessary to promote natriuresis and correction of hyponatremia in patients with severe heart failure treated with captopril; the renal vascular action of captopril enhances the effectiveness of furosemide.