ABSTRACT— Histologic sequences in the liver of rodents exposed by inhalation to gaseous vinyl chloride were compared to the lesions in man exposed to the same agent, mainly in vinyl chloride polymerization plants. An identical sequence, starting with circumscribed proliferation of hepatocytes, soon followed by proliferation of a variety of sinusoidal cells and frequently associated with sinusoidal dilatation, progresses to intralobular and more frequently to trabecular angiosarcoma. Predominantly in young animals and rarely in man, hepatocellular carcinoma develops, but never cirrhosis. The sequence represents a dynamic process of competition between proliferating hepatocytes and sinusoidal cells, of hepatocytes with fibroplasia, between perisinusoidal fibrosis and sinusoidal dilatation, and of proliferation of various sinusoidal cells versus angiosarcoma. The great similarity in the evolution in man and rodents, rarely encountered in other experimental models, supports the prediction of human cancer from animal experiments. The precursor nodules differ from the nodules commonly observed in hepatocarcinogenesis by co-proliferation of sinusoidal cells. The differences in the reactions between man and rodents bespeak a strong fibroblastic reactivity in man. Most important, the precursor lesion of mixed hepatocellular and sinusoidal cell proliferation may be of diagnostic value, being superior to conventional hepatic tests in detection of some initial environmental lesions.