The topography of renal injury after ischemia-reflow was studied in intact rats by clamping the right renal artery for variable periods of time and examining the histologic appearance of the kidney in large 1-mu plastic sections. As reported by others, the straight portion of the proximal tubule (S3) was especially susceptible to ischemia-reflow injury. The pattern of focal necrosis produced in S3 by short (15-30-minute) and longer (45-60-minute) periods of arterial occlusion appeared related to gradients to oxygenation during reflow, in that more extensive injury was seen in areas remote from blood vessels, while perivascular tubules were protected. A similar pattern was seen in S1 and S2 after a longer period (45-60-minutes) of ischemia, which produced extensive but incomplete necrosis in these convoluted segments, with protected tubules lying within zones surrounding arcuate and interlobular arteries. The immediate postglomerular portion of S1, a tubular segment normally well supplied with oxygen, was an exception to this rule. Selective necrosis limited to this portion of the nephron appeared after only 15-30 minutes of ischemia, recalling the special sensitivity of S1 cells to inhibition of mitochondrial respiration. These results suggest that in different segments of the proximal tubule, injury after ischemia-reflow is determined not only by changes that occur during complete ischemia but also by the adequacy of oxygenation during the reflow period.