Intercellular adhesion molecule-1, strongly expressed on the interlobular and proliferating bile ducts in primary biliary cirrhosis, is important in the migration and adhesion of inflammatory cells from the circulation to these structures. A soluble form has been found to be elevated in serum in primary biliary cirrhosis. Our aim was to check on the role of soluble intercellular adhesion molecule-1 in primary biliary cirrhosis with particular reference to its specificity by comparison with other disease control groups and to assess its relationship with stage of disease activity, circulating lymphocyte activation and cholestasis. Soluble intercellular adhesion molecule-1 (enzymelinked immunosorbent assay) and liver biochemistry were measured in 41 patients with primary biliary cirrhosis, 9 with primary sclerosing cholangitis, 12 with alcoholic liver disease and 17 healthy controls. In subgroups of patients with primary biliary cirrhosis, lymphocyte activation and hepatic bile acid uptake and excretory rates were determined. Soluble intercellular adhesion molecule-1 was significantly higher in all three disease groups. Levels in primary biliary cirrhosis and primary sclerosing cholangitis were similar and significantly higher than alcoholic liver disease. Soluble intercellular adhesion molecule-1 expression was greater in late primary biliary cirrhosis than early disease and correlated with histological progression. Correlations were also found with alkaline phosphatase, y-glutamyl transpeptidase and conjugated bilirubin. A trend toward an inverse correlation with hepatic excretory rate was found, but no correlation was detected with circulating lymphocyte interleukin-2 receptor expression. We conclude that serum soluble in-