Urine contains high concentrations of epidermal growth factor (EGF), and EGF is a potent growth promoter for proximal tubular cells. In the present study, urinary and whole-kidney EGF levels were investigated in rats with mercuric chloride (HgCl2)-induced acute renal failure (ARF) using a specific radioimmunoassay for rat EGF to clarify changes in EGF after toxic injury. Male Wistar rats were given HgCl2 (2 mg/kg, subcutaneously) or saline. Serum urea nitrogen and creatinine levels were measured for 4 days after toxin administration. Forty-eight hours after toxic injury, urinary immunoreactive EGF levels in HgCl2-treated rats decreased significantly compared with control rats (1.62 ± 0.15 versus 3.78 ± 0.21 ng/mg creatinine; p < 0.01). Urinary immunoreactive EGF was at its lowest level 96 h after toxic injury (0.64 ± 0.06 ng/mg creatinine; p < 0.001). Twenty-four hours after toxic injury, renal immunoreactive EGF levels increased significantly compared with control rats (22.04 ± 2.12 versus 4.84 ± 0.70 ng/g wet weight tissue; p < 0.001), and the increase persisted for as long as 48 h (13.36 ± 1.61 ng/g wet weight tissue; p < 0.05). In summary, urinary immunoreactive EGF levels decreased and renal EGF levels increased in rats with HgCl2-induced ARF. These findings suggest that there is an impairment in the excretion of EGF in rats with HgCl2-induced ARF and that local paracrine production of EGF continues i