SUMMARYPig to dog renal heterografts are excellent models of hyperacute rejection of transplanted organs, since the dog has a potent cytotoxic antibody against porcine cells. Lymphocytotoxicity, hemagglutinating activity, and platelet-agglutinating activity can be demonstrated when dog serum is incubated with the appropriate pig cells. The major functional derangement observed during hyperacute rejection of renal transplants is a drastic diminution in blood flow to %o of normal levels within minutes following transplantation while there is a corresponding increase in renal resistance to 50 times normal values. Minimal changes in interstitial pressure and renal weight corroborate angiographic findings showing failure to fill interlobular arteries. The occlusive process appears to be related to endothelial sloughing and platelet and leukocyte plugs within arterioles. Ninety to 95% of platelets and 80-83% of leukocytes in renal arterial blood are retained by the kidney during hyperacute rejection. The number of platelets and leukocytes in renal vein blood decreases dramatically and correlates significantly with the reduction in renal blood flow (r=0.95 and 0.98, respectively). Most of the leukocytes retained are neutrophils. Erythrocytes are also retained within the kidney. There is no evidence of release of histamine, serotonin, or bradykinin. Heparinization does not alter the rejection reaction. It is therefore, concluded that a major mechanism of immunological injury during antibody-mediated hyperacute rejection of pig to dog renal heterografts is the formation of platelet and leukocyte thrombi which occlude the interlobular vessels and produce cortical ischemia and necrosis.