We compared the accessory cell function of human alveolar macrophages (AM) to that of human blood monocytes (Mo) obtained by bronchoalveolar lavage and venipuncture from normal volunteers. Graded numbers of either AM or Mo were added to autologous peripheral blood T lymphocytes that were stimulated with a purified protein derivative of tuberculin (PPD). Either AM or Mo were cocultured with allogeneic T lymphocytes in mixed lymphocyte reaction (MLR) experiments. Both AM and Mo supported the PPD-induced T lymphocyte proliferation and allogeneic MLR at low ratios of AM or Mo to T lymphocytes with similar efficiency. However, AM showed marked suppressive effects at higher ratios of AM to T lymphocytes (1:1). PPD-pulsed AM, but not AM killed by physical treatments (heat, freeze-thaw, sonication), induced T lymphocyte proliferation. An indirect immunofluorescent study demonstrated that most AM express HLA-DR antigens. Furthermore, AM synthesized DR antigens with molecular weights of 33,000 and 29,000-31,000 daltons. When AM were treated with both anti-DR monoclonal antibody and complement, PPD-induced T lymphocyte proliferation and MLR were diminished. These results suggest that human AM function as accessory cells in the antigen-induced T lymphocyte proliferation and DR antigens on AM play an important role in the accessory cell function.