Acute effects of MK421 were examined in 11 male normal volunteers. Oral administration of 5 mg of MK421 did not induce any changes in blood pressure or pulse rate. Plasma renin activity increased significantly from 7.3 +/- 2.9 ng/ml to 22.2 +/- 7.1 (p less than 0.05), whereas plasma aldosterone concentration did not change. Blood kinin, or urinary excretion of kallikrein and of prostaglandin E did not change. However, urinary excretion of sodium increased significantly from 44.0 +/- 6.8 mEq/4 hr to 56.5 +/- 6.5 (p less than 0.02) following the administration of MK421. The present results show that an increased renin release induced by MK421 is independent of change in blood pressure, and also suggest that MK421 may have a direct action on the renal tubules.