Utilizing a new technique of in vitro arterial perfusion, renal allo-transplant rejection in the inbred rat has been studied. The earliest changes of rejection are detected on day 5 and these consist of scattered, nonperfused areas of cortex. This is consistent with physiological studies showing a normal Hippuran clearance at day 3 after allotransplantation and reduced at day 5 in this same model. By day 7, no cortical filling is observed; at, this time the Hippuran clearance is that of anephric rats. It is concluded that the earliest vascular lesion of functional significance which occurs during allotransplant rejection in this model is located in the preglomerular arterial supply of the cortex.