Wistar rats are susceptible to the induction of experimental autoimmune thyroiditis (EAT) and recently a cloned Wistar thyroid epithelial cell line (WRT) has become available. In this study we have examined the in vitro proliferative response of Wistar rat lymphoid cells to the WRT cells as a model for better understanding thyroid cell-T cell interactions. Lymph node (LN) cells from normal Wistar rats showed an early and vigorous response to syngeneic thyroid cells (WRT). Further examination of the Wistar phenomenon revealed that unpurified lymphoid cells were also able to mount a proliferative response to rat thyroglobulin. The Wistar LN cell response to WRT cells consisted of T cell proliferation that was both MHC class I and class II restricted. There was a greater proliferation of CD8+ than CD4+ T cells, but WRT-stimulated lymphoblast cells were not cytotoxic to 51Cr-labeled WRT cell targets. These data suggest that normal Wistar rats have circulating thyroid-specific T cells that may be related to their known susceptibility to EAT. Furthermore, the interaction between such thyroid-specific T cells and cloned syngeneic thyroid cells offers a unique model for the further investigation of thyroid-immune interactions and the escape from tolerance induction.