To clarify the clinical significance of vitronectin, we compared the concentration of plasma vitronectin with serum fibrous markers and liver function test values in patients with chronic liver diseases. We also evaluated the vitronectin content in the liver by means of enzyme-linked immunosorbent assay and the localization of vitronectin in liver tissue with enzyme immunohistochemistry. In chronic liver disease, the concentration of plasma vitronectin was significantly lower than that in healthy controls, being related to the severity of liver disease. The plasma levels of vitronectin showed no correlation to fibrous markers but a significant correlation with those of serum albumin and prothrombin time. On the other hand, the content of vitronectin in liver tissue was significantly increased in chronic liver disease compared with that in normal controls. In the normal liver, vitronectin was observed in the portal area by light microscopy. In chronic hepatitis and cirrhosis, vitronectin was found in the connective tissue around the portal and central veins and in the areas of piecemeal and focal necrosis. These findings suggested that vitronectin is deposited in injured tissue through the process of repair and fibrosis and plays an important role as an adhesive protein. Moreover, the lower levels of plasma vitronectin in chronic liver disease may be due to its decreased synthesis, deposition or both in injured tissue. (HEPATOLOGY 1994;20:1412-1417.) Vitronectin is an adhesive glycoprotein in the extracellular matrix and plasma and has been shown to bind with collagen and heparin (1). It has important physiological actions in cell adhesion (2, 3), cell necrosis mediated by complement action (4, 5) and blood coagulation (61, but little is known about its distribution and