Graft biopsy was performed in 49 cases of acute rejection in which plasma creatinine levels had not decreased after a first course of high-dose intravenous methylprednisolone. The severity of the histological picture was defined as mild, moderate, severe, or irreversible. In most patients with a mild picture renal function returned to normal; about one half of the cases with moderate lesions recovered; all patients but 1 with a severe or irreversible histological picture rapidly lost the graft. A significant correlation was also found between an unfavorable clinical outcome and the degree of some features such as: arterial intimal proliferation, arterial fibrinoid necrosis, glomerular necrosis, interstitial erythrocyte extravasation and peritubular capillary congestion. It is suggested that in a difficult clinical condition such as an acute rejection not responding to a course of high-dose steroid administration, graft biopsy may generally offer a reliable prognostic index for further therapy.