Using murine (T,G)-A--L-reactive T cell clones, we have demonstrated the existence of unique homozygous antigen-presenting determinants expressed on C57bl/6 mice, controlled by the I-A subregion of the murine major histocompatibility complex (MHC), which are not expressed on semisyngeneic (C57Bl/6 x A/J)F1 [(B6A)F1] cells. Additionally, we were able to demonstrate that there exist (T,G)-A--L-reactive clones in F1 mice derived between low responder and high responder parents [(B6A)F1] that recognize antigen in association with transcomplementing hybrid I-A subregion determinants expressed uniquely on (B6A)F1 cells not expressed on cells of either of the parental strains. These data suggest that phenotypic high responsiveness exhibited by (higher responder x low responder)F1 mice was not simply controlled by the high responder parental genome, but was controlled at the phenotypic level of expression of antigen-presenting determinants. Such antigen-presenting determinants can be created by complementation using products of the low responder as well as high responder genome. The significance of the existence of such F1 specific hybrid antigen-presenting determinants for T cell specificity and recognition of self was discussed.