The diuretic response of patients with congestive heart failure to establish doses of diapamide (750 mg) and furosemide (80 mg) was compared in an open, crossover study. Peak urine output occurred in the first 6 hours after administration of furosemide but somewhat later (12 to 18 hours) with diapamide. Both agents produced active diuresis and natriuresis in most patients. Comparisons of drug effect during the first days of each treatment period and analysis of the entire first treatment period indicated that urine output with furosemide was significantly greater than with diapamide. Urinary sodium excretion on the first day of treatment was not significantly greater with furosemide than with diapamide, nor were the differences significant on subsequent days. The observed differences between drugs on urinary potassium and chloride excretion were not statistically significant. The most frequently occurring adverse reaction was mild to moderate nausea, which was reported by five patients receiving diapamide and two patients receiving furosemide. Diarrhea and vomiting were also more frequent with diapamide. Diapamide would appear to serve a role between the milder thiazide diuretics and the more effective furosemide.