It is well known that angiotensin-converting enzyme inhibitors attenuate progressive ventricular enlargement or hypertrophy after myocardial infarction and that cardiac angiotensin-converting enzyme activity is increased in the rat model of myocardial infarction. In this study, to determine whether the beneficial effects of angiotensin-converting enzyme inhibition on cardiac hypertrophy after myocardial infarction are due to a reduction in ventricular afterload or to inhibition of cardiac angiotensin-converting enzyme, we used sodium loading during angiotensin-converting enzyme inhibition. The rat model of myocardial infarction was treated with a vehicle, 1% saline, as drinking fluid, perindopril (2 mg/kg/day), or 1% saline as drinking fluid plus perindopril (2 mg/kg/day) for 6 weeks. Perindopril reduced blood pressure, prevented cardiac hypertrophy, and inhibited cardiac angiotensin-converting enzyme. The effects of perindopril on blood pressure and cardiac hypertrophy were abolished by sodium loading, which did not alter the degree of cardiac angiotensin-converting enzyme inhibition. Thus the actions of perindopril on cardiac hypertrophy depend more on blood pressure reduction than on cardiac angiotensin-converting enzyme inhibition in the rat model of myocardial infarction.