Autoreactive IL-2-producing T-cell hybridomas were established from New Zealand Black and White (B/W) F1 and MRL/1 mice. In B/WF1 mice the frequency of IL-2-producing hybridomas increased with age. It is necessary for the cells to recognize autologous MHC molecules in order to release IL-2. Inoculation of hybridoma cells into several mouse strains via the footpad produced significant swelling responses in an H-2-restricted manner. Finally, several autoimmune abnormalities were induced in naive H-2-compatible mice by i.v. inoculation of certain hybridoma cells. These results demonstrate that self-MHC molecule recognition by T cells plays an important role in the development of autoimmunity.