AbstractHuman lymphocyte function antigen (HLFA) is a cell surface protein defined by two monoclonal antibodies MHM23 and MHM24. It is present on both B and T lymphocytes but in greater amounts on the latter. Both antibodies precipitated antigen, from radiolabeled HSB‐2 cells, which ran as two chains on sodium dodecyl sulfate polyacrylamide gel electrophoresis at 180 and 94 kDa. Neither antibody inhibited binding of the other, indicating that distinct epitopes were recognized. Both antibodies were shown to inhibit HLA‐restricted lysis of influenza virus‐infected and Epstein‐Barr virus‐transformed target cells by cytotoxic T lymphocytes. Blocking occurred at the level of the effector cells and in the presence of subsaturating concentrations of antibody. Both reagents also inhibited lysis of K562 cells, mediated by natural killer cells. These blocking effects differ from the inhibitory effects of monoclonal anti‐HLA ABC and anti‐suppressor cytotoxic T cell antibodies which inhibit only HLA‐restricted lysis when present in saturating amounts. It is concluded therefore that HLFA is likely to be involved in the nonspecific adherence or lytic functions of killer cells rather than specific anti