Recently, procedures have been developed for the selective enrichment (positive selection) and depletion (negative selection) of alloantigen-reactive lymphocytes. These procedures will be applied to two questions concerning the biological function of gene products of the major histocompatibility complex (MHC) and the high frequency of MHC alloantigen reactive T lymphocytes: (1) the extent of involvement of MHC gene products in the induction and expression of certain T-cell mediated immune functions, namely cytotoxicity, delayed-type hypersensitivity and helper responses for B cells; and (2) the possible involvement of anti-MHC receptors present on the majority of T cells in the specificity of triggering with conventional antigens. These questions have a direct bearing on the mechanisms of T-cell stimulation by antigen and whether T cells possess multiple specificities for antigen.