Using a syngeneic Wistar rat model we have shown that the Wistar rat thyroid (WRT) cell line causes significant and specific proliferation of lymph node T cells from normal Wistar rats, and of splenic T cells from a thyroiditis prone line of BB/W rats, when cultured in the presence of irradiated feeder cells. These T cell responses were associated with a marked increase in the number of CD8+T cells. However, using normal Wistar rat T cells which had been previously exposed to WRT cells, rested and then re-exposed to WRT cells as antigen, we consistently found that the T cell population had been rendered unreactive, or anergic, to further thyroid cell stimulation. However, if recombinant rat IL-2 was added to the cultures, then T cell responsivity was seen on re-exposure to WRT cells. The lymphopenic BB/W rat also had T cells which showed a primary T cell response to the WRT cell line accompanied by a marked increase in CD8+T cells. In contrast to the Wistar rat T cells, the BB/W T cells retained a proliferative responsiveness to WRT cells on re-exposure although such responsiveness could also be markedly enhanced with IL-2. These data suggested that antigen-mediated inhibitory signals were induced in normal Wistar rat T cells by the syngeneic WRT cell line, independent of the presence of co-stimulatory molecules. Furthermore, the thyroiditis prone BB/W rat T cells appeared to be less responsive to such anergy induction, perhaps contributing to their susceptibility to autoimmune thyroid disease.