Approximately 50% of Wistar "BB" rats spontaneously develop overt diabetes mellitus characterized by loss of beta-cells and "insulitis." To define abnormalities of immunoregulation in these rats, we quantitated their major circulating lymphocyte subsets. Independent of the development of diabetes, we found the BB rats to have a markedly increased percentage of circulating B lymphocytes which is secondary to a severe T-cell lymphocytes which is secondary to a severe T-cell lymphocytopenia, with the major circulating T-cell subset reacting with monoclonal antibody W3/25 markedly decreased. This lymphocytopenia is present in every animal studied and contrasted with studies of the nondiabetic Wistar strain from which the "BB" rats were developed.