By means of double diffusion in gel reactions, "heterophile" antibodies were demonstrated in human renal transplantation sera. Of thirty-two recipients of renal allografts, 12 (37 per cent) had antibodies to extract of bovine erythrocyte stromata, and 5 (19 per cent) of 26 recipients produced antibodies to extract of sheep erythrocyte stromata. These antibodies became detectable 1-6 months after transplantation and persisted for several months or years. However, the strength of reactions given by individual serum samples from the same recipient varied considerably. Sera from the same recipient gave a reaction of identify, while sera from two different recipients frequently gave reactions of partial identity or nonidentity. The antibodies reacting with bovine stroma extract were distinct from those reacting with sheep stroma extract. Evidence was also presented that the heterophile antibodies in transplantation sera are different from Paul-Bunnell antibodies in infectious mononucleosis sera. Some of the HL-A typing sera were shown to contain antibodies against bovine stroma extract. The antigen recognized by these sera in the bovine stroma extract was not related to any HL-A specificity. Three of eight rabbits which received skin and renal allografts formed antibodies against bovine stroma extract. Absorption studies clearly demonstrated that these antibodies are directed against antigens present in the donor's, but not in the recipient's tissues.