The appearance of alpha-smooth-muscle-actin (alpha-smA)-positive cells during hepatic fibrosis was studied immunohistochemically in rat and human livers. In the normal rat liver, alpha-smA was observed only in vascular smooth muscle cells. With the progression of fibrosis induced by CCl4 injection, alpha-smA-positive cells appeared in the perisinusoidal space and the fibrous septa, and ultimately surrounded regenerative nodules. An increase of desmin-positive cells was recognized in the fibrotic areas and the perisinusoidal area. In the human liver, alpha-smA-positive cells appeared in the fibrotic area, whereas no desmin-positive cells were observed, except in vascular walls of the central vein and the portal tract, alpha-smA is a good marker for the detection of myofibroblast-like cells, and the appearance of alpha-smA in liver mesenchymal cells seems closely related to the process of hepatic fibrosis in both rat and man.