Anti-beta 2 microglobulin sera (beta2m AS) rendered specific after extensive absorptions were obtained following immunization of rabbits with highly purified beta2m prepared from urine of tubular proteinuria. beta2m AS were cytotoxic upon addition of selected rabbit complement for human T and B lymphocytes. Partial inhibition of sheep red blood cells receptor recognition on T lymphocytes (E rosettes) and C3 component recognition on B lymphocytes (EAC rosettes) was obtained only with high concentrations of Fab'2 anti-beta2m, eliminating a direct association of beta2m and those receptors. Fab'2 anti-beta2 induced very little inhibition of Fc portion receptor recognition (EA rosettes), but they had no effect on lysis of targets covered with IgG anti-targets (ADCC), a function mediated through that receptor. Anti-beta2m antibodies in excess inhibited antigen-induced proliferation (PPD) and the mixed lymphocyte reaction (MLR) performed in AB serum and fetal calf serum containing media ; whereas a potentiation of the response occurred in the presence of an antigen excess (beta2m) brought by the culture medium (AB serum) suggesting involvement of immune complexes. Pretreatment of responding cells with beta2m AS did block unilateral MLR ; conversely, treatement of stimulating cells had no effect. Independent migration of T cell membrane antigens (HTLA) and beta2m upon addition of suitable ligands, as well as the lack of inhibition by Fab'2 anti-beta2m of complement dependent lysis with IgG anti-HTLA, excluded possible association of HTLA and beta2m.