Patients with severe congestive heart failure (New York Heart Association [NYHA] functional classes III-IV) often can tolerate only low doses of angiotensin-converting enzyme (ACE) inhibitors because pronounced hypotension caused by additional ACE inhibitor increments may decrease renal perfusion. The use of high-dose loop diuretics is currently advised to overcome diuretic resistance in refractory congestive heart failure (CHF). In a baseline controlled study, we evaluated 21 patients with diuretic resistance and evident fluid retention for the responses to 5 days of double drug therapy consisting of high-dose loop diuretic (10 mg oral bumetanide) in combination with the maximum tolerable dose of an ACE inhibitor (individualized to blood pressure and kidney function). Five patients (24%) showed a gross natriuresis and reduction in excess weight > 25% in response to this therapy. The remaining 16 patients (76%) with insufficient responses (i.e., < 25% reduction in excess weight) subsequently received 100 mg spironolactone once a day for 7 days in addition to the double therapy. Spironolactone coadministration was highly effective in 13 of 16 patients (81%). Marked natriuresis and diuresis were achieved within the next week of treatment, and CHF symptoms regressed or disappeared. The clinical course was similar in the bumetanide-ACE inhibitor and the bumetanide-ACE inhibitor-spironolactone treatment (triple therapy) groups. Plasma aldosterone was significantly higher (p < 0.05) in the patients who needed spironolactone. The 3 patients who were considered refractory to triple therapy exhibited the highest baseline plasma aldosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)