Comparative effects of angiotensin converting enzyme inhibitors and calcium channel blockers were assessed in rats infused chronically with synthetic endothelin. When 50 mg/kg/day of captopril orally or 6 mg/kg/day of enalapril intraperitoneally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 142.7 +/- 5.9 mmHg (p less than 0.05) or 128.7 +/- 6.7 mmHg (p less than 0.05), respectively, compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of captopril or enalapril was sustained for the entire experimental period and was not associated with a significant change in urinary sodium excretion, whereas both drugs induced a significant increase in urine volume. Chronic infusion of angiotensin II intraperitoneally at a subpressor dose (400 micrograms/kg/day) reversed the antihypertensive effect of captopril in endothelin-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine orally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 137.0 +/- 2.4 mmHg (p less than 0.05) or 119.7 +/- 5.9 mmHg (p less than 0.05), respectively, compared to the rise when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. These results indicate that the reduced sensitivity of the peripheral arteries to endothelin may be involved in the mechanism of the hypotensive action of angiotensin converting enzyme inhibitors, dependent on the suppressed angiotensin II formation.