The long-term effects of losartan, an angiotensin II subtype-I receptor antagonist, were compared with those of captopril in a murine model of dilated cardiomyopathy caused by encephalomyocarditis virus. Four weeks after viral inoculation, 42 DBA/2 mice were given oral losartan 1.2 mg/kg/day (n = 8), 12 mg/kg/day (n = 8) or 60 mg/kg/day (n = 8) or captopril 7.5 mg/kg/day (n = 8) in drinking water or distilled water (n = 10). Mice were killed at the end of the 12-wk treatment period. Heart weight, left ventricular thickness, left ventricular cavity dimension and myocardial fiber diameter were significantly lower in mice given losartan 60 mg/kg as compared with the infected untreated group. Captopril had a similar effect on all parameters. The pathologic score of cardiac fibrosis was significantly lower in the mice treated with captopril but was not reduced in the mice treated with losartan. Moreover, as compared with the age- and sex-matched normal mice, cardiac mass and myocardial fiber diameter were significantly lower in normal mice treated with losartan 60 mg/kg. This study suggests that long-term treatment with losartan may prevent thickening of left ventricular wall and cavity dimension in dilated cardiomyopathy caused by encephalomyocarditis virus. The potency, and perhaps the efficacy, of losartan appear to be less than those of captopril.