The cellular basis of tolerance induction to Mls-encoded antigens in radiation bone marrow (BM) chimeras has been investigated in two H-2-compatible strain combinations of AKR/J (H-2k, Thy-1.1, Mls-Ia) and C3H/He (H-2k, Thy-1.2, Mls-IIa). Sequential appearance of host- and donor-derived T cell subsets and T cell receptor gene messages occurred in the peripheral lymphoid organs of both irradiated AKR/J mice reconstituted with C3H/He BM cells (C3H/He-AKR/J chimera) and irradiated C3H/He mice reconstituted with AKR/J BM cells (AKR/J-C3H/He chimera). A large number of cells expressing T cell receptor gamma genes were detected in spleen on day 21 after reconstitution, while the normal level of alloreactivity was first detected in the spleen on day 56 after reconstitution in correlation with the appearance of appreciable levels of Thy-1 high cells and T cell receptor alpha and beta gene transcripts. T cells bearing V beta 6, that is strongly correlated with reactivity to antigens encoded by the Mls-Ia genetic locus, were virtually abolished in spleen on day 56 in both C3H/He-AKR/J chimera and AKR/J-C3H/He chimera. Furthermore, expression of V beta 3 gene transcripts, that are important for recognizing Mls-IIa, was undetected either in the peripheral lymphoid cells of AKR/J-C3H/He chimera or in those of C3H/He-AKR/J chimera. These results suggested that clonal elimination of self-reactive T cells bearing V beta 3 or V beta 6 was induced by both host-derived radioresistant cells and donor-derived repopulating cells in the thymus of radiation BM chimeras.