Anti-HLA alloantisera inhibit mixed lymphocyte responses in which normal lymphocytes are used as stimulator cells. These same antisera are unable to inhibit lymphocyte proliferative responses stimulated by lymphoblastoid cells from cultured lymphoid cell lines. They also fail to inhibit either the generation of cytotoxic effector cells by lymphoblastoid cells or lymphocyte-mediated cytotoxicity against the lymphoblasts. Although the number of HLA antigens on the surface of lymphoblasts is reported to be greater than on normal lymphocytes, the failure of alloantisera to inhibit lymphoblast-induced responses in vitro does not appear to be due to insufficient amounts of antiserum to react with the antigenic sites. Rather, the data are interpreted to suggest that antigens which are not HLA and are not closely associated with HLA on the lymphocyte membrane are responsible for the stimulation of allogeneic lymphocytes by lymphoblastoid cells. Although lymphoid cell lines are known to contain the genome of the Epstein-Barr virus, antisera against products of the viral genome fail to inhibit proliferative responses to lymphoblastoid cells, suggesting that these antigens do not directly participate in lymphocyte activation.