Approximately 50% of BB rats develop insulinopenic hyperglycaemia and ketosis spontaneously in association with insulitis. Amelioration of the syndrome by immunosuppression suggests a cell mediated immune pathogenesis. Analysis of the cell-mediated immune profile of overtly diabetic and normoglycaemic diabetes prone BB rats indicates that they are lymphocytopenic relative to non-diabetes prone BB rats and that the T cell pool is particularly affected. Furthermore, lymphocytes from diabetic and diabetes prone BB rats, while producing normal responses to the T cell mitogen concanavalin A, do not respond when mixed in vitro with major histocompatibility complex incompatible lymphocytes. This anergy is not restored either by enriching the responding cell population for T cells or by adding exogenous T cell growth promoting factor. Thus BB rats have a numerical and regulatory deficit of their T cells which could be related to their propensity for diabetes.