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The proliferation of neoplastic and nonneoplastic hepatocytes is caused by various humoral growth factors with autocrine and paracrine mechanisms, and the proliferative activity of both hepatocytes and nonhepatocytic cells contributes to neoplastic growth. The authors attempted to detect various kinds of proliferating cells immunohistochemically in small hepatocellular carcinoma (HCC) using a monoclonal antibody against DNA polymerase alpha. Most of the HCC cells that stained for this enzyme were small, had basophilic cytoplasm with poorly developed organelles, and aggregated to form clusters distributed randomly within cancer nests. Nonhepatocytic cells also were stained, including some endothelial cells, Kupffer's cells, macrophages, and lymphocytes. Fat-storing cells were not stained. The number of stained sinusoidal (capillary) cells decreased in this order: Kupffer's cells and macrophages, endothelial cells, and fat-storing cells. Nonhepatocytic cells, including lymphocytes, proliferated more actively in areas with actively growing HCC cells than in those with quiescent cancer cells. The relationship between stained HCC cells and stained sinusoidal cells was clearly defined; the correlation coefficient was 0.97. These findings suggest the possibility of a relationship between the proliferative activity of neoplastic hepatocytes and that of sinusoidal cells, including lymphocytes. Cancer 1992; 69:2433-2439.