Evidence indicates that after vascular occlusion, infusion of angiotensin II restores blood supply to ischemic tissues by stimulating the development of collateral circulation through a mechanism independent of the mechanical effects of increased blood pressure. To test this effect in focal cerebral ischemia, angiotensin II was intravenously administered for four hours to gerbils immediately after unilateral carotid ligation. Three different pressor doses, 50, 250, and 500 ng/kg/min, were used, and mortality rate was evaluated at 1 and 2 days after vascular occlusion. Two additional groups similarly prepared were infused either with saline or with the pressor agent metaraminol. There was a significant inverse relationship between the infusion dose of angiotensin II and mortality: the greater the infusion dose of angiotensin II, the lower the mortality rate. Infusion of metaraminol, at the dose chosen to mimic the pressor effect of the highest angiotensin II dose, yielded a mortality rate which was statistically indistinguishable from that obtained with saline infusion. It is concluded that the mortality rate after unilateral carotid occlusion is significantly reduced by intravenous administration of angiotensin II through mechanisms unrelated to its hypertensive action. Evidence suggests that this may occur by the enhancement of the development of collateral circulation and therefore the reduction of the severity of brain ischemia.