This study was designed to investigate the effects of ATP-MgCl2 when infused immediately 8 or 24 hr after 45 min of bilateral renal artery ischemia and to determine if an initial improvement in clearance of inulin (C(In)) would be sustained throughout the course of recovery. In addition, the influence of ATP-MgCl2 on the pattern of recovery of whole kidney and single nephron function was assessed by determining the impact of this agent on proximal tubular pressure and transepithelial backleak. The postischemic administration of ATP-MgCl2 resulted in significantly enhanced recovery of C(In) irrespective of the time of the infusion after the initial insult. This beneficial effect was sustained in that the ATP-MgCl2-treated rats had significantly better C(In) 1, 3 and 7 days after the injury when compared to normal saline-treated animals. Moreover, single nephron inulin clearance (SNC(In)) was better preserved than whole kidney C(In) in both groups of animals and in the ATP-MgCl2-treated animals SNC(In) was similar to control values even 1 day after the injury. The enhanced recovery of single nephron function in the ATP-MgCl2-treated animals resulted from reduced proximal tubular pressure and diminished blackleak of tubular fluid. Animals given ATP-MgCl2 had better preservation of cellular morphology. Horseradish peroxidase was excluded from most epithelial cells and the interstitium in a manner similar to that seen in control animals while saline-treated rats demonstrated backleak of this tracer compound. Based on these studies, it appears that the beneficial effect of ATP-MgCl2 occurs because of the preservation of sublethally injured cells by augmentation of the process of recovery.