Enalapril (MK-421), a new angiotensin converting enzyme inhibitor, reduces the blood pressure in one-kidney, one-clip hypertensive rats at 30 mg/kg p.o. (n = 12). On the fifth day and during the fifth week after renal artery constriction, systolic blood pressure decreased from 196 +/- 4 and 240 +/- 5 mm Hg pretreatment to 159 +/- 8 and 225 +/- 3 mm Hg, respectively (p less than 0.001 and 0.05, respectively) and was maintained at this level for about 8 h. Serum angiotensin converting enzyme activity was significantly inhibited by enalapril. Similarly, enalapril (30 mg/kg p.o.) in two-kidney, one-clip hypertensive rats (n = 18) on the fifth day and during the fifth week after operation resulted in a decrease in blood pressure from 162 +/- 5 and 217 +/- 5 mm Hg to 117 +/- 6 and 120 +/- 7 mm Hg, respectively, to the preoperative normotensive level (113 +/- 1 mm Hg). These results indicate that the renin-angiotensin system may play an important role in the pathogenesis of two-kidney, one-clip hypertensive rats. However, in the pathogenesis of one-kidney, one-clip hypertensive rats, other mechanisms seem to be involved besides the renin-angiotensin system.