Summary In the early period following radical hepatectomy for hepatoma, recurrences in the remaining liver are frequently found. In regenerating liver, implantation and growth of tumour cells released into the portal system during surgical treatment might be promoted. We examined the relationship between liver regeneration and the formation of metastases following hepatic resection. Intraportal injections of rat ascites containing hepatoma AH130 cells at a concentration of 1 x IO' cells 0.2 ml-l were made at various periods following two thirds liver resection in rats. Tumour cell injections immediately at 24 h after surgery resulted in an increased number of hepatic metastases compared with control animals. Tumour cell injections 2 weeks after hepatectomy, however, had no significant difference in effect compared with control rats. In contrast, tumour cells injected immediately after removal of half of the caudate lobe resulted in the same number of metastases as control animals. These results demonstrate that the number of artificially induced hepatic metastases was increased during an initial period of active liver regeneration and was proportional to the volume of hepatectomy.The effect of 5-fluorouracil (5FU) or mitomycin C (MMC) as inhibitors of hepatic regeneration on liver metastasis after hepatectomy was studied. The administration of 5FU (20mg kg-') or MMC (0.2 mg kg-') immediately, 24 and 48 h after hepatectomy resulted in a marked reduction in metastatic lesions. The administration of 5FU caused delays in weight gain and decreases in the wet weight of remaining liver, while MMC had no effect on either. Accordingly, results of 5FU administration may be due to inhibitory effects on liver regeneration whilst that of MMC administration may be due to cytocidal antitumour effect. The effect of OK-432 as an immunoactivator on the implantation and growth of tumour cells in regenerating liver was also studied. Pretreatment with OK-432, 0.5 mg intraperitoneally on 7 consecutive days, had no effect on hepatic metastases.The pathophysiology of liver regeneration may enhance hematogenous hepatic metastasis and release of tumour cells during surgical manipulation may represent an important cause of recurrence following hepatic resection.Recent advances in preoperative diagnostic techniques and intraoperative ultrasonography have provided a greater ability to determine the number, location, and extent of liver lesions (Kanematsu et al., 1985; Makuuchi et al., 1987). Despite their application to the surgical resection of liver malignancies, however, recurrences are frequently found in the early postoperative period. It as yet remains unclear whether such lesions are due to pre-existing microscopic disease, result from surgical manipulation, or both.According to Okuda et al. (1977), intrahepatic arterioportal anastomosis is demonstrated in 63.2% of patients with hepatocellular carcinoma, and retrograde flow of the portal vein trunk is seen in 25.4% as revealed by angiography. Therefore, tumour cell release into the p...