Following 70% hepatectomy, male Sprague-Dawley strain rats were given purified human plasma fibronectin and/or aprotinin intraperitoneally after hepatectomy and were divided into 4 groups: Group FA (40 mg/kg of FN and 25,000 KIU/kg of aprotinin), Group F (40 mg/kg of fibronectin), Group A (25,000 KIU/kg of aprotinin), and Group C which served as a control. The liver regeneration rate 72 hours after hepatectomy in Groups FA and F, and the plasma FN levels at 24 and 72 hours following hepatectomy in groups with FN, were significantly higher than that of the control group. The incorporation of 3H-thymidine into DNA and the phagocytic index of the reticuloendothelial system at 24 hours in Groups FA and F, and the mitotic index at 72 hours after hepatectomy in Group FA were significantly increased as compared to the control. But the supplementation of 20 mg/kg of indomethacin to the 4 groups resulted in significant suppression of 3H-thymidine uptake 24 hours after hepatectomy. Moreover, plasma fibronectin levels in rats correlated well with the phagocytic index and DNA synthesis 24 hours following partial hepatectomy. These results suggest that fibronectin may act as an activator of the reticuloendothelial system, related to prostaglandins, in the process of liver regeneration.