The special features of liver sinusoidal endothelium (LSE) are crucial for normal liver physiology. Cirrhotic livers, especially in primary biliary cirrhosis (PBC), are characterized by transformation of the LSE into a continuous, vascular type. The transformation is important for disease progression and explains some of the pathological hallmarks of the cirrhotic liver. Here, we investigated the presence of liver sinusoidal endothelial cell (LSEC)-reactive autoantibodies (Abs) in the sera of patients with autoimmune liver diseases, and assessed the ability of these Abs to transform LSE into vascular endothelium. Compared to healthy individuals (9%), significantly higher numbers of patients with PBC (59%; P < 0.001) and autoimmune hepatitis (AIH) (32%; P < 0.05) had Abs against LSECs. Incubation of primary LSEC cultures with F(ab')(2) fragments of anti-LSEC Abs isolated from sera of patients with PBC and AIH, induced 1) cell surface expression of vascular endothelium-associated markers, CD31, and factor VIII-related antigen; 2) significant production of fibronectin, laminin and collagen type IV; 3) loss of fenestrae, formation of tight junctions and Weibel-Palade bodies. Deposition of immunoglobulins on LSECs were found in liver biopsies of AIH and PBC patients. Thus, anti-LSEC autoAbs transform LSE into a vascular type and may therefore play an important role in the development of hepatocellular failure and portal hypertension in PBC and AIH patients.