We have obtained data from various investigations that firmly establishes an important host defense function for human C-reactive protein (CRP). In transgenic mice, the beneficial effect of CRP depends largely on its ability to recruit complement, Fc gamma receptors and the adaptive immune system; but this function is not limited to the blood-borne protein nor does it require a substantial rise in blood CRP levels. Moreover, in clinical studies, we have observed that differences in baseline levels of CRP among individuals correlate with a polymorphism in the CRP gene. The relevance of this finding is underlined by the observation that subtle elevation of blood CRP is associated with significantly increased risk of cardiac disease.