Evidence is presented that skin-reacting transplantation antibodies (SRTA) can be elicited not only by skin allografts, but also by injection of dispersed allogeneic lymphoid cells. Two mechanisms of action of SRTA, which are not mutually exclusive, are compatible with the experimental results. (1) SRTA may act as homocytotropic antibodies, producing skin reactions by fixing to the skin of the test animal and combining with circulating antigens brought to the test site. (2) SRTA may produce skin reactions by combining directly with “sessile” antigens in the skin. Genetic studies showed that the antigens combining with SRTA are inherited as simple Mendelian traits. Furthermore, it was shown that these antigens are not related to the major rat histocompatibility antigens, Ag-B, nor are they related to any other described rat alloantigen system. Thus, the antigens responsible for SRTA belong to a new antigenic system.