To examine the effects of angiotensin-converting enzyme (ACE) inhibitor and aldosterone antagonist on myocardial collagen in the cardiomyopathic hamster, the collagen concentration was measured by determining the hydroxyproline concentration, and the ratio of type I to type III collagen (type I/III ratio) was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Five-week-old Bio14.6 cardiomyopathic hamsters were treated with the ACE inhibitor captopril (20 mg/kg per day) or the aldosterone antagonist K-canrenoate (20 mg/kg per day) in drinking water for 20 weeks, and the collagen concentration and type I/III ratio at 25 weeks were compared with those in 25-week-old untreated Bio14.6 and normal F1b hamsters. The collagen concentration markedly increased and the type I/III ratio significantly decreased (ie, type III collagen dominant) in untreated Bio14.6 compared with F1b at 25 weeks. Captopril and K-canrenoate treatment significantly reduced the collagen concentration and reversed the changes in the type I/III ratio in cardiomyopathic hamster. These results suggest that ACE inhibitor and aldosterone antagonist improve myocardial collagen in the cardiomyopathic hamster, not only quantitatively but also qualitatively, and that the mechanism of this improvement may be related to the cardiac renin-angiotensin-aldosterone system.