Alloreactive T cells represent a relatively large fraction of the T cell population compared with the fraction of T cells that are specific for other foreign Ag. Recent findings indicate that most alloreactive T cells recognize endogenous peptides in association with a non-self MHC product. In light of these observations, it is perhaps not surprising that previous studies of the size of the TCR-alpha beta repertoire among alloreactive cells showed that they express many different V alpha and V beta genes. To further access the extent of diversity among alloreactive cells, we examined V alpha J alpha combinatorial diversity in polyclonal populations of a BALB/c anti-BALB.B mixed lymphocyte response. A long term culture from naive mice contained a diverse repertoire of V alpha J alpha combinations that was similar to the diversity present among unstimulated splenic T cells. In contrast, long term cultures from hyperimmunized animals contained "dominant" clones of T cells that expressed a restricted repertoire of V alpha J alpha combinations. Examination of the nucleotide sequences of these alpha-chains suggested that there was selective expansion of T cells with identical alpha-chains. In addition, T cells that express the same V alpha J alpha combination but different junctions were also identified. Consistent with previous results, the isolates from hyperimmune animals did not contain somatic mutations in the CDR3 region of the alpha-chains. Nevertheless, the results suggest that T cells may be subject to in vivo selection and clonal expansion analogous to the process of affinity maturation of Ig.