The natriuretic and diuretic effects of combined treatment with furosemide and metolazone have been studied quantitatively. 15 hospitalized patients with severe fluid retention who showed no reduction of body weight despite treatment with furosemide received metolazone in addition for 3 days. 11 patients had biventricular heart failure with edema, and 4 had cirrhosis of the liver with ascites. Following the addition of metolazone at a starting dose of 2.5 mg/d, a highly significant increase in diuresis and natriuresis, with a corresponding reduction in body weight, was seen in all patients pretreated with a daily dose of 40-370 mg furosemide (mean 122 mg/d). On the first day of this combined treatment the mean sodium excretion increased from 131 to 303 mval/d (2 p less than 0.01) and the mean urine volume increased from 1677 to 2940 ml/d (2 p less than 0.01). The mean reduction in body weight was 6.1 kg (2 p less than 0.001) within 7 days of continuous treatment. Even at low doses metolazone significantly potentiates the diuretic effects of furosemide and therefore simplifies the treatment of fluid retention. High doses of furosemide can be avoided in many cases, a factor of particular advantage in ambulatory long term therapy and in patients with decreased kidney function. It may also lower the cost of the therapy. In 3 patients the furosemide dose had to be lowered after metolazone was started, to avoid an excessive negative fluid balance. These cases clearly demonstrate the importance of daily checks on the patient's body weight after starting combined therapy with furosemide and metolazone.