Background This study evaluated the independent and combined effects of captopril and carvedilol on left ventricular remodeling in chronic heart failure. Although angiotensin-converting enzyme inhibitors and b-blockers are known to attenuate the remodeling process in chronic heart failure, a direct comparison of these agents has not been performed. Methods We investigated 57 patients with mild to moderate chronic heart failure (48 ischemic, 9 nonischemic) who were randomized in a double-blind fashion to treatment with carvedilol or captopril at maximum doses of 25 mg twice daily for 3 months, followed by 3 months of combined treatment. Serial echocardiography, right heart catheterization, and treadmill exercise testing were performed at baseline, 3 months, and 6 months. After exclusions, 49 patients were evaluated during monotherapy and 48 during combination therapy. Results Carvedilol monotherapy produced significant reductions in end-systolic volume, leading to a greater median increase in ejection fraction compared with captopril monotherapy (4.7% vs 1.5%, respectively; P <.05). Each drug caused similar reductions in left ventricular mass, chamber sphericity, and pulmonary artery wedge pressure during monotherapy and combined treatment. Adjunctive treatment with carvedilol produced a trend toward a greater increase in ejection fraction (4.3% vs 2.7%, respectively; P not significant) and significantly greater reductions in the wall thickening score index than with captopril (0.25 vs 0.08, respectively; P =.04). Conclusions Although angiotensin-converting enzyme inhibitor therapy did not alter left ventricular volume, treatment with carvedilol was associated with reductions in chamber volume; both drugs reduced left ventricular mass and sphericity. These beneficial effects on remodeling may help to explain the relative prognostic benefits of these therapies. (Am Heart J 2001;142:704-13.)