Reports of a large number of biological activities of the acute phase reactant C-reactive protein (CRP) (1,2) and its association with a variety of blood borne cells (3,4), led us to a study of the expression of CRP by human peripheral blood cells (PBL) using two kinds of CRP-reactive monoclonal antibodies. We had previously described a reaction of CRP with a monoclonal antiidiotype antibody to a murine phosphocholine (PCh) binding myeloma protein (5). Of another group of monoclonal antibodies obtained by immunizing mice with human CRP, three were shown to react with human CRP in a Ca++-dependent manner while a fourth reacted with CRP independently of calcium and binding of this antibody was also not blocked with PCh (6). Initial experiments showed that one of these site specific antibodies also reacted with a proportion of normal human peripheral blood cells. We then showed that this subpopulation included 100% of human monocytes suggesting that a CRP-like determinant exists on the surface of human monocytes but not on other lymphoid or NK cells or granulocyte populations.