The function of the reticuloendothelial system (RES) was evaluated after the inoculation of an experimental tumor in rats. Four groups were studied according to tumor size and site. Reticuloendothelial function was evaluated by measuring the biokinetics of a standardized [99Tcm]-sulfur colloid. Estimation of the uptake rate of the labeled colloid into the liver and other parts of the RES was performed through the use of a two-compartment model. Animals with small liver or subcutaneous tumors showed an increased activity of both the hepatic and the extrahepatic RES. Animals with large retroperitoneal tumors showed a significant decrease in the RE function of the liver. In these animals the function of the extrahepatic RES was not changed compared to controls but was, however, significantly decreased compared to animals with smaller tumors. The findings may reflect a difference in the impact of tumor size on RE function extra- and intrahepatically.