Deletion of self-reactive T cells in the thymus is probably the most important mechanism for the establishment of tolerance (reviewed in von Boehmer et al. 1990). In addition to this central tolerance there is also the need for peripheral tolerance mechanisms for cells having escaped thymic deletion, eg because the antigen is not represented in the thymus or is not present in high enough amounts. Peripheral tolerance appears to be particularly important for MHC class I-reactive T cells (CD8^) because these recognize only antigens synthesized by the respective target cells themselves. Thus, antigens produced only in the periphery and which may have access to the thymus will not feed into the MHC class I presentation pathway. In contrast, soluble antigens can be taken up by MHC class Il-positive cells and induce thymic tolerance (Kyewiski et al. 1984). It is also unlikely that shedded MHC class I molecules carrying a particular peptide can travel to the thymus and cause thymic tolerance because transgenic mice expressing a soluble MHC class I molecule were not tolerant for this class I molecule in the CD8 compartment (Arnold et a!. 1989). Therefore, as described below, we have concentrated on the induction of peripheral tolerance for an MHC class I model antigen, the H-2K*'molecule.