We have previously produced a monoclonal antibody (mAb), B1D6, reactive with a 37 kD placental IgG Fc-binding molecule (FcR), recently identified as annexin II. Annexin II is an intracellular molecule found in several cell types, including endothelium and monocytes. Since soluble Fc-binding molecules are of importance in the regulation of the immune response, we have now used B1D6 in a competitive ELISA to study levels of soluble annexin II in human sera. Soluble annexin II was detected in all sera studied. The highest levels were observed in patients with infectious mononucleosis. Gel filtration of sera revealed annexin II in fractions corresponding to a molecular weight of 40-60 kD. In Western blot analysis a molecule of approximately 37 kD was found. The pI of soluble annexin II was about 7.5-8 as demonstrated by chromatofocusing. Annexin II belongs to a family of phospholipid-binding molecules involved in anti-inflammatory responses, and elevated levels of annexin II in serum may be important for the suppression of an immune response.