The T cell reactivity against type II collagen (CII) was analyzed in the collagen‐induced arthritis‐susceptible mouse strain DBA/1. It was shown that the proliferative response in lymph node cells from rat CII‐immunized mice was mainly directed against a foreign determinant present on all heterologous CII tested but not on autologous CII. A T cell line with this reactivity reacted with high sensitivity with CII and the determinant was mapped to the CB11 fragment of CII. A weak autoreactive response could be detected in the primary cultures using high concentrations of mouse CII and this reactivity remained after several stimulations with high concentrations of rat CII but not with low concentrations of rat CII. A similar response against mouse CII but with only limited cross‐reactivity to rat CII was seen when culturing the cells with mouse CII as antigen. The optimal concentration for the autoreactive response was always more than 100‐fold higher than for the response of the T cells specific for heterologous CII. An anti‐CII T cell response could also be detected in spleen cells from unimmunized mice and the strongest response was obtained using autologous CII. These results suggest that T cells recognizing self CII are normally activated in the DBA/1 mouse and possibly as a consequence exhibit a clonal anergy pattern with a weak proliferative response only at high concentrations of CII.