Restoring kidney function after injury involves cell migration and proliferation, processes that are yet to be precisely defined. Because epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) promote recovery from acute renal failure, we used SV-40 immortalized human proximal tubule cells to examine the effects of these growth factors on cell proliferation after peroxide injury (1.5 mM for 1 hour). ATP levels decreased to approximately 15% of control values immediately after injury but returned to nearly normal levels after 4 hours of recovery. Under control conditions, both EGF and IGF-1 stimulated proliferation and their effects were additive. However, 20-24 hours after injury, while IGF-1 stimulated proliferation, EGF was no longer effective nor was the combination of EGF and IGF-1. Although the EGF receptor was decreased 20 hours after injury, the lack of IGF-1 effect could not be explained by loss of the IGF-1 receptor, which remained unchanged after peroxide injury. Thus, the mechanism responsible for the blunting of the IGF-1 effect on proliferation following injury remains speculative. However, we conclude that the effects of growth factors under control conditions may not predict their effects after injury.