These experiments were designed to determine the influence of age on the response of the kidney to ischemia. Renal ischemia was induced in female Fischer-344 rats, 3-4 or 37-38 months old, by renal arterial and venous occlusion followed by 0, 1, 24, or 96 hr of reflow. Age-matched controls were sham operated but were not subjected to ischemia. A transient postischemic increase in blood urea nitrogen (BUN) and serum creatinine was observed in young rats. In old rats, BUN and serum creatinine remained markedly elevated through 96 hr postischemia. In vitro renal cortical slice accumulation of organic ions was inhibited to a greater extent in old rats than in young rats 96 hr postischemia. Histologically, renal tubular damage was more severe in old than in young rats 24 and 96 hr postischemia. Tubular regenerative activity was similar in old and young rats at 96 hr, but restoration of tubular architecture was more complete in young rats. Organic ion accumulation by renal cortical slices from naive old rats was inhibited by in vitro anoxia (treatment with 100% N2) to a greater extent than tissue from young rats. These data suggest that old rats are more susceptible to renal ischemia than are young rats and these differences in susceptibility may reflect intrinsic age-related differences in basal renal metabolism.