Monocytes/macrophages expressing an epitope recognized by a monoclonal antibody 27E10 are present in acute but are absent in chronic inflammatory disorders. This report shows that the 27E10 antigen is formed by noncovalent association of the two Ca²⁺‐binding proteins MRP8 and MRP14 which belong to the S100 protein family. Identification has been confirmed immunochemically, by matrix‐assisted UV‐laser desorption/ionization spectrometry and by partial amino acid sequencing. Surface expression of the MRP8/MRP14 complex on a subset of monocytes is reported for the first time and shown to be up‐regulated in a Ca²⁺‐dependent manner. The 27E10 surface‐positive monocytes isolated by cell separation techniques release high amounts of tumor necrosis factor‐α and interleukin‐1β in contrast to their 27E10 surface‐negative counterparts thus emphasizing their role in inflammation.