MLR suppressor factor (MLR-SF) optimally suppresses MLR responses only of responder cells which are compatible in the I-C subregion with cells producing the factor. Therefore, presence of MHC-encoded determinants on MLR-SF has been investigated, with particular interest in I-C, as well as the possible role of I-J determinants. Suppressor activity of supernates of alloantigen-activated spleen cells was tested after passage over solid immunoadsorbants prepared with various anti-H-2 subregion sera. Immunoadsorbants with specificity towards K and D region products were ineffective while several preparations with I region specificity removed suppressor activity from factors of the appropriate haplotype. The single subregion specificity common to all adsorbing preparations was I-C. Recently, ambiguity has developed with regard to genetic resolution of I-C and adjacent subregions, including difficulties of serologic differentiation of I-C products of the k and d haplotypes. Antisera prepared in I-Ck/I-Cd disparate strain combinations have identified T cell restricted determinants which are distinct between these haplotypes.