Stimulation of interleukin-1 (11-1) in peripheral blood monocytes exposed to Creactive protein (CRP) and C-reactive protein-platelet-activating factor (CRP-PAF) complexes was demonstrated in vitro in this study. Significant synthesis of intracellular IL-l12-5-foId increases in the number of adherent monocytes as determined by indirect immunofluorescence using rabbit anti-IL-1 and goat antirabbit IgG-fluorescein isothiocynate, was shown. Both CRP alone (10 pglml) and especially CRP-PAF mixture (10 pg CRPll ug PAFlml) showed maximum stimulation of IL-1 of 41 and 95 cellsllO field examined, respectively. CRP alone examined in a dose-response study showed optimum stimulation of IL-1 production at the 1 pglml concentration with 57% of monocytes showing fluorescence. CRP at varying concentrations with a con-stant amount of PAF (1 pglml) showed optimum IL-1 staining monocytes (63%) with CRP at 10 pglml (10 pg CRPll pg PAF). Similar significant enhanced extracellular IL-1 production by monocytes exposed to CRP and CRP/PAF mixtures was shown by the mouse thymocyte assay. Supernatants of monocytes exposed to CRP (10 pglml) or CRP-PAF (10 p g l l pglml) demonstrated mouse IL-1 synthesis of 92 and 110 stimulation indices in the thymocyte assay, respectively. It is suggested that CRP and especially CRP-PAF complexes activate macrophage through their appropriate receptors to production of monokines which modulate the immune system. Thus, CRP appears to function nonspecifically in a behavior reminiscent of specific immunoglobulins.