Renal transplants in adult dogs (23 first-set homografts and 11 autografts) were removed at 12 hours to 7 days after transplantation and studied histologically and immunocytochemically. The rejection of renal homografts is associated with an infiltrate of lymphocytes, hemocytoblasts and immature and mature plasma cells containing gamma globulin. Beginning at 3 to 4 days the interlobular arteries down to the afferent arterioles show a focal, progressive degeneration with media vacuolization and necrosis, and at 5 to 6 days endothelial proliferation and thrombosis set in. Coincidentally, in the altered vessels small droplets contain only γ-globulin which can be eluted with an acid buffer and binds in vitro complement, suggesting that the γ-globulin is part of an antigen-antibody complex. Hypothetically, antibody is formed in response to antigen from the graft in the rejection of kidney homografts. Then antigen-antibody complexes, localized or formed in the walls of small blood vessels, cause necrosis and endothelial proliferation that result in thrombosis and tissue necrosis which terminates the rejection.