A large proportion of T blasts activated in the mixed lymphocyte reaction (MLR) is capable of binding plasma membrane (PM) vesicles prepared from the stimulator strain1,2. The binding of vesicles is specific, and the antigens recognized are serologically detectable H-2K, D and I region products3,4. T blasts binding stimulator K (and D) antigens belong to the Lyt 1 -2+ subclass, whereas those binding stimulator Ia antigens are Lyt 1 +1- (ref. 5). We report here that antibodies against heavy chain V-region determinants (VH) 6, and furthermore, monoclonal7 or conventional antibodies against responder cell Ia determinants strongly inhibit the binding of radiolabelled stimulator vesicles. Anti-responder Ia inhibition is restricted to the Lyt 1 +2- subset of T blasts and correlates with a weak expression of Ia determinants on these cells. The relevant Ia determinants are not resynthesized after trypsin treatment of the blasts. In these conditions anti-VH, but not anti-Ia reagents inhibit stimulator vesicle binding. Trypsinized T blasts can, however, passively absorb Ia material from supernatants of syngeneic, lipopolysaccharide (LPS)-activated spleen cells, and thus regain their susceptibility to vesicle-binding inhibition with anti-Ia sera. Acquisition of syngeneic Ia is also blocked by the anti-VH reagent. We conclude that Lyt 1 +2- MLR blasts possess binding sites for both allogeneic (stimulator) and syngeneic Ia antigens.