The influence of class I MHC gene products on selection of the L3T4+ T helper cell repertoire was investigated. It was found that the generation of immune responses specific for Kbm6 class determinants involved L3T4+ T helper cells specific for a composite MHC determinant composed of I-Ab + Kbm6 determinants. Most interestingly, it was found that the selection of L3T4+ T helper cells specific for IAb + Kbm6 composite determinants required intra-thymic expression of I-Ab + Kb composite MHC determinants. In other words the selection of Ia- restricted Th cells specific for mutant class I determinants required expression by intrathymic cellular elements of self-class II and self class I MHC determinants. This is the first example of class I and class II gene complementation involved in the selection of the T cell repertoire.