Vein allografts were studied in the rat using the major histocompatibility complex-incompatible DA and Lewis inbred strains. Allografts were performed in the Lewis to DA and DA to Lewis combinations, with Lewis to Lewis isografts serving as controls. Vein grafts were performed by interposing a 1 cm length of fresh iliolumbar vein into a defect of the iliac artery, using microsurgical techniques. The grafts were under observation for 18 weeks for (1) patency, (2) gross structural changes, (3) histological changes, and (4) antibody responses. No immunosuppression was used. All grafts remained patient throughout the period of observation, although aneurysm formation was noted in some allografts toward the end of the observation period. Histologically, allografts and isografts were indistinguishable. In the first 2 weeks, they showed patchy areas of necrosis in the vein walls, with subsequent intimal hyperplasia and medial fibrosis. In both strain combinations a lymphocytotoxin response was induced in most animals, the response being particularly strong in the DA to Lewis combination. All cytotoxic activity could be absorbed out using red blood cells, suggesting that the specificity of the antibody was mainly or entirely directed against SD antigens.