SUMMARYRabbits were sensitized with multiple sequential skin allografts and then challenged with kidney grafts. Rejection, characterized by its rapid tempo and by accumulation of polymorphonuclear neutrophils and/or renal cortical necrosis, occurred in all 12 animals which received renal grafts, against which they had the corresponding transplantation antibodies, detectable by means of the mixed agglutination test with cell cultures. Four grafts were in situ long enough for renal cortical necrosis to develop. The necrosis involved the entire outer cortex, but only an occasional glomerulus contained a few strands of fibrin. For comparison, the generalized Shwartzman reaction (gSr) was induced by infusion of ehdotoxin into seven normal rabbits. Here, the renal cortical necrosis was characterized by the sparing of some nephrons in the outer cortex and by occlusion of all of the glomerular capillaries in the necrotic areas. In the grafts, lipid stains revealed large amounts of fat in the interlobular arteries but none in the glomeruli, while in the gSr only the glomeruli were involved, suggesting different levels of vascular obstruction in the two lesions. Circulating fibrin degradation products were present in only one of eight grafted rabbits but were present in all seven rabbits with the gSr. All eight grafts placed into rabbits which did not have the corresponding antibodies showed rejection characterized by a mononuclear cell infiltration but no significant fibrin deposition or fat accumulation. Circulating fibrin breakdown products were detected in none of these rabbits. Finally, kidney allografts were given to nine normal rabbits. The production of the gSr in these rabbits at a time when the graft was in the process of rejection showed that such grafts were less vulnerable to the noxious effects of an endotoxin infusion than were the recipients' own kidneys.