Inbred strains of rats can currently be classified into eight Ag-B groups. Within an Ag-B group, individual strains generally share identity both the Ag-B histocompatibility antigens and mixed lymphocyte responses. In this report we present data from three strains which are Ag-B and mixed lymphocyte reaction (MLR) disparate: KGH (Ag-B7, MLR-1), MNR (Ag-B4, MLR-5), and B3 (Ag-B3, MLR-4). Popliteal lymph node assays involving these three strains and standard inbred strains demonstrate that the graft-versus-host reaction and MLR reactions in the rat are closely related. Positive graft-versus-host reactions were observed only in strain combinations incompatible for the MLR and were unaffected by differences in their Ag-B histocompatibility antigens. The close association of the MLR and graft-versus-host reaction provides additional evidence that the Ag-B/MLR disparity in these strains is the result of natural genetic recombinations within the major histocompatibility complex.