Chickens of the Iowa State S1 line have been selected for ability to regress Rous sarcoma virus-induced (RSV) tumors, humoral immune response to GAT (Ir-GAT), and erythrocyte antigen B. Sublines homozygous at the major histocompatibility complex (MHC), as well as F1 heterozygotes and F2 segregants, were tested for resistance to fowl cholera by challenge with Pasteurella multocida strain X73. Control of the response at high doses was associated in a preliminary study with Ir-GAT and response to RSV tumors. Genetic control of resistance to low doses of P. multocida was demonstrated via sublines and F2 segregants to be linked with genes of the B-Gregion. Thus, genetic control of resistance to fowl cholera in chickens after exposure to Pasteurella multocida was shown to be linked to the major histocompatibility B complex, in this first demonstration of MHC-linked resistance to bacterial disease challenge.