Ischemic acute renal failure is principally a disease of the elderly, but the effect of aging on renal susceptibility to ischemic damage has not been defined. To address this issue, adolescent (3-4 months), mature (12-13 months), and aged (24-25 months) rats underwent base-line renal functional assessments, and then they were subjected to a standardized ischemic event (37-minute, bilateral renal artery occlusion). The loss of renal function [assessed by azotemia and creatinine clearance, (Ccr)] and the severity of tubular damage (necrosis, casts) were determined 24 hours later. Base-line functional assessments indicated no significant differences in Ccr/100 gm body weight between the groups, but urinary protein excretion increased with age (p less than 0.001). In response to renal artery occlusion, the adolescent, mature, and aged rats lost 59 +/- 4, 82 +/- 4, and 94 +/- 1% of their base-line Ccr (p less than 0.01), respectively. Among the proteinuric rats, no correlation was noted between percent loss Ccr and urinary protein excretion. Despite the large differences in postischemic renal function, the extent of tubular morphologic damage did not differ among the groups. The percent loss Ccr did not correlate with necrosis (r = -0.02) or casts (r = 0.07). Although focal glomerulosclerosis and mild tubular atrophy were noted in the aged kidneys these lesions were minimal to absent in the mature rats. We conclude that aging increases susceptibility to severe ischemic acute renal failure in the rat, an effect that is apparent even during a transition from the adolescent to the mature state. This finding cannot be simply ascribed to increasing proteinuria, a loss of renal functional reserve, or to increased tubular morphologic damage. The data are most consistent with the view that underlying age-related glomerular/hemodynamic changes lead to an exaggerated functional decline in response to ischemic renal injury.