Migration-stimulating factor (MSF) is a novel angiogenic factor present in most breast tumours but not in normal breast . The purpose of this study is to ascertain the presence of MSF in serum and to determine its possible value for breast cancer diagnosis and prognosis. MSF bioactivity has been detected in the serum of 90% (27/30) of breast cancer patients, compared with 13% (4/30) of healthy controls. MSF-specific antibodies have enabled the identification of MSF in serum using immunoprecipitation and ELISA. Unexpectedly, quantification of immunoreactive MSF in serum showed no difference between cancer patients and controls. This discrepancy between bioactive MSF and immunoreactive MSF is due to the presence of two forms of MSF in serum, as well as a potent inhibitor of MSF (MSFI). Two isoforms of MSF have been cloned; these differ by a 15-amino-acid deletion and are referred to as MSF+aa and MSF-aa. MSF isolated from control serum behaves like rhMSF+aa, in that it is inhibited by MSFI and therefore is not bioactive in serum. MSF from cancer patient serum and rhMSF-aa are not inhibited by MSFI, and are bioactive in serum. Our next goal is to ascertain the biochemical difference between patient and control MSF and to assess the diagnostic and prognostic value of MSF-based serum measurements.