Cellular and vascular proliferation in the perisinusoidal area of the acinar zone III of the liver preceded the formation of septal fibrosis in rats repeatedly treated with intraperitoneal injections of pig serum. Deposition of type I, III, IV and V collagens and increased amounts of fibronectin and laminin were also observed. Immunochemical staining for actin, elastin and desmin better disclosed the rich vascularization of the fibrous septa. Hypertrophy and hyperplasia of sinusoidal fat-storing cells point to the main role of such cells in the process of septum formation, but other connective tissue cells, such as mast-cells, were also present. These changes seemed to result from stimulation of the sinusoidal macrophage/fat-storing-cell system by foreign material present in the pig serum. The model may be useful for further studies on pathogenesis of septal fibrosis of the liver.