An attempt was made to determine whether 36 long-term kidney homograft recipients and their donors were compatible for 7 major leukocyte groups. It was found that 21 of these recipients were surviving 2 to 3 years in spite of incompatibility for 1 or 2 major leukocyte antigens. Survival of mismatched grafts does not itself indicate that the antigens being measured are not transplantation antigens, for it was shown that the 15 recipients with no groups of mismatch were clinically superior to those with group incompatibilities. Moreover, histopathologic scores given to biopsy specimens taken 2 to 3 years after transplantation were significantly correlated with the number of group mismatches. Because the leukocyte groups were determined by cytotoxicity reactions of peripheral blood lymphocytes, the results may have been influenced considerably by chimerism in chronically dialyzed uremic patients or change in lymphocyte antigenicity or susceptibility to lysis upon prolonged immunosuppressive treatment. Although the possibility of these complications could not be ruled out in all instances, it was shown that 52 dialyzed uremic patients and 49 patients who had been treated with immunosuppression for over 1 year did not possess more or less antigens than a random population of normal individuals. It is concluded that: (1) the major leukocyte antigens are histocompatibility antigens and (2) since survival can be attained at times despite mismatches for these groups, the antigens are of intermediate strength and kidney homograft rejection may occur if excessive numbers of antigens are incompatible or if particular combinations of antigens are mismatched.