The effect of combined hydrochlorothiazide and furosemide therapy was studied in eight hypertensive patients with renal insufficiency who had poor response to either furosemide or hydrochlorothiazide alone. The study was divided into two parts. In part A, five patients had an inadequate response to furosemide in doses of 160 to 240 mg/day followed a strict protocol in order to compare the effect of increased doses of furosemide with combined hydrochlorothiazide-furosemide administration. All had azotemia, presumable from nephrosclerosis, and had serum creatinine concentrations ranging from 2.3 to 4.9 mg/dl. Four of the five patients had inadequate arterial pressure control, and the remaining patients had fluid retention from the administration of minoxidil. In all five patients, plasma volume was either increased or normal, despite long-term treatment with furosemide. Increasing the dose of furosemide to between 320 and 480 mg/day had only a modest additional diuretic effect, and plasma volume and arterial pressure were not significantly changed. Adding hydrochlorothiazide, 25 to 50 mg twice a day, produced a marked diuresis, and a significant reduction in weight, plasma volume and mean arterial pressure (p less than 0.025 for all three patients). In part B, combined hydrochlorothiazide-furosemide therapy was used to treat three additional patients who had an inadequate response to either diuretic alone. The results indicate that combined hydrochlorothiazide-furosemide is a potent diuretic regimen and is effective in many patients wit chronic renal failure who have a poor response to furosemide alone.