Summary Pregnancy-associated plasma protein A (PAPP-A), metalloglycoprotein isolated from pregnancy serum, has been also found in different cell systems (vascular cells of smooth muscle, osteoblasts…). Two forms exist: a high-molecular-weight heterotetrameric complex particularly during pregnancy, and an active free form. PAPP-A has been found to proteolytically cleave insulin-like growth factor (IGFBP-4). Automated techniques have been developed particularly for use in prenatal Down's syndrome (DS) screening. Serum PAPP-A concentrations increase during pregnancy, and decreased PAPP-A values have been found to be associated with fetal DS. It is used, in association with free βhCG and measurement of nuchal translucency, in first trimester DS screening. PAPP-A has also been used as a marker of aneuploidies or preeclampsia and predictor of adverse outcome. Moreover, PAPP-A has been described as a marker of instability of atherosclerotic plaque activity and might predict complications in cardiology. But this application requires more sensitive tests in comparison with prenatal diagnosis.