The adhesion molecule ICAM-1 mediates leucocyte adhesion to target structures and other immune cells by binding with the leucocyte adhesion receptors LFA-1 and MAC-1. During rejection of human liver transplants there is increased expression of ICAM-1 on target structures such as bile ducts and venous endothelium and also on lymphocytes infiltrating the graft. Recent reports suggest that a soluble, functionally active form of ICAM-1 designated circulating ICAM-1 (cICAM-1) is released by activated lymphocytes and might be an important mechanism for modulating lymphocyte adhesion and the inflammatory process. We detected cICAM-1 in bile and serum after liver transplantation using an enzyme-linked immunosorbent assay. Serum cICAM-1 was elevated early in the course of acute rejection and appeared at the same time as the soluble interleukin-2 receptor, a marker of lymphocyte activation. Serum levels, however, were not specific for rejection since they were also elevated in infective complications. In contradistinction, biliary levels of cICAM-1 were only elevated in rejection and appeared to be due to local release/secretion within the liver. These data demonstrate that cICAM-1 is released within the liver during graft rejection, probably from activated lymphocytes, and support previous studies that suggested that factors in bile reflect immunological activity within the liver graft more closely than serum factors.