Background and Aims: Endotoxin-responsive monocytes/macrophages (CD14-positive) are potential sources of profibrogenic factors. The aims of this study were to determine (1) whether hepatic CD14-positive cells are present in various forms of chronic liver disease, and (2) the relationship between CD14-positive cells, myofibroblasts, and fibrosis in these diseases.Methods: Liver specimens from control subjects (n=12) and those with primary biliary cirrhosis (n=18), chronic hepatitis C (n=13), or nonalcoholic steatohepatitis (n=13) were immunostained for CD14, CD68, and alpha-smooth muscle actin (SMA) and the number of cells expressing these antigens was determined. Fibrosis and inflammation were also assessed.Results: The total number of hepatic CD68-positive cells was similar in diseased and control livers. The number of CD14-positive cells was increased in advanced fibrosis in primary biliary cirrhosis and hepatitis C but not in nonalcoholic steatohepatitis. The number of CD14-positive cells was also increased in hepatitis C specimens with high inflammatory activity. CD14-positive cells were often associated with alpha-SMA-positive myofibroblasts in fibrous septa.Conclusions: The number of hepatic CD14-positive cells is increased in advanced fibrosis in subjects with primary biliary cirrhosis and hepatitis C but not in nonalcoholic steatohepatitis. In primary biliary cirrhosis and hepatitis C, CD14-positive macrophages are found in close proximity to fibrous septa and myofibroblasts. In hepatitis C, an increased number of CD14-positive cells are associated with high inflammatory activity.