Although CD4 antigen is expressed on monocytes (MO), its functional role is uncharacterized. In this study, isolated human MO were separated into CD4+ and CD4- MO subsets and assessed for presentation of tetanus toxoid. The CD4- MO subset had decreased antigen presenting cell (APC) capacity as well as increased PGE2 production when compared to the CD4+ MO subset. Addition of a cyclo-oxygenase inhibitor (Indomethacin) did not restore the CD4- MO subset's APC capacity to that of the similarly treated CD4+ MO subset, eliminating differential PGE2 production as the primary cause of differential APC capacity. Production of monokines such as IL-1 and plasminogen activator, which affect APC capacity, was similar in the CD4 MO subsets. However, tumor necrosis factor (TNF) production (IFN gamma plus MDP-induced) of the CD4+ MO subset was slightly greater than that of the CD4- MO. CD4- MO's lower APC capacity is not totally explained by their differential IL-1, TNF, or PGE2 production.