C-reactive protein (CRP), a trace serum protein that increases markedly in concentration during inflammatory reactions, was recently shown to bind to a subset of human IgG-FcR-bearing peripheral blood lymphocytes in the presence of a ligand such as pneumococcal C-polysaccharide (CPS). CRP has also been detected on a small percentage of PBL that are associated with NK activity. In the present study, we assessed the effects of CRP and CRP-CPS complexes on a variety of human lymphocyte functions in vitro. CRP and CRP complexes significantly enhanced (generally two to threefold) cell-mediated cytotoxicity, minimally enhanced the MLC reaction, and induced a small but regularly detectable blastogenic response in resting PBL. CRP or CRP-CPS complexes had no effect on mitogen-induced blastogenesis, PWM-induced generation of IgM plaque-forming cells, E-rosette formation, antibody-dependent cell-mediated cytotoxicity, or NK activity. The basis for the preferential ability of CRP to enhance cytotoxicity responses in vitro is under further investigation.