The purpose of this study was to determine that the administration of an angiotensin converting enzyme (ACE) inhibitor enalapril would confer protection against doxorubicin-induced experimental heart failure, and attenuate the development of left ventricular dysfunction. Seventeen dogs were chronically instrumented with an intracoronary catheter and received doxorubicin weekly for 4 weeks. Animals were assigned to two groups: group 1: untreated heart failure; and group 2: simultaneous enalapril administration (5 mg twice a week). Hemodynamic data were obtained at week 0 and 12. Echocardiography was performed weekly. Survival improved with simultaneous enalapril administration (36% in group 1 vs. 100% in group 2, P=0.04). The increase in the left ventricular end-diastolic pressure was significantly reduced at week 12 (17+/-1 mmHg in group 1 vs. 9+/-1 mmHg in group 2, P=0.0042). The fall in left ventricular stroke work index was significantly prevented (52% in group 1 vs. 21% in group 2, P=0.006). The increase in right ventricular end-diastolic diameter was significantly reduced by enalapril prophylaxis. Simultaneous treatment with enalapril was beneficial in the prevention of doxorubicin-induced cardiomyopathy. Copyright 2002 European Society of Cardiology