The effects of ethanol and its metabolites on collagen synthesis in cultured rat Ito cells and hepatocytes were studied. In cultured Ito cells, collagen synthetic ability reached peak values after incubation for 24 h and after 8 h in cultured hepatocytes. The distribution patterns of 14C-activity in each collagen fraction were quite different between the two cell types. About 80% of the activity was found in the degraded collagen fraction in the cultured hepatocytes, indicating a rapid turn-over of collagen protein in this cell type. In the Ito cells, the activity in the intact collagen was about 50%. Ethanol and its metabolites added to the incubation medium did not stimulate collagen synthesis in either cell type; rather, they inhibited it. Collagen metabolism in the cells to which ethanol or its metabolites had been added was slower than in the control medium. These results indicate that the pathogenesis of alcoholic liver fibrosis is not simple and that interaction or modulation of cell function in different types of cells should be considered when examining the mechanisms of fibrogenesis in alcoholic liver fibrosis.