Residual tumor in the remnant liver after partial hepatectomy (PH) for colorectal liver metastases is a serious clinical problem. This fact is reflected by the high number of recurrences after potentially curative liver resections. Liver regeneration, it appears, might influence the growth of remaining micrometastases in the liver. Using rats, we demonstrated enhancement of growth of a syngeneic colon carcinoma (CC 531) in the remnant liver after 70% PH. Fourteen days after PH, tumor weights in the liver were twice as high as those of sham-operated rats. This difference in tumor weight was not found in extrahepatic tumors. In vitro experiments did not show stimulation of cultured CC 531 cells by portal or systemic serum withdrawn 24 hours or 14 days after hepatectomy as compared with sera obtained after sham operation. Co-cultures of CC 531 cells and hepatocytes (in ratios of 1:10 or 1:1) demonstrated a higher 3H-thymidine incorporation than was the case in separately cultured cells. In co-cultures, bromodeoxyuridine (BrdU) incorporation in DNA was found primarily in CC 531 cells and rarely in hepatocytes. Cell density appeared to be of influence on 3H-thymidine incorporation in co-cultures. Hepatocytes were found to have a stimulating effect on CC 531 cells in low-density cultures, whereas high-density cultures exhibited an inhibiting effect after a culture time of 120 hours. These results show that, depending on cell density in co-cultures, a paracrine stimulating influence of hepatocytes on this type of colon carcinoma cells (CC 531) might be responsible for the increased tumor growth in vivo. (HEPATOLOGY 1995; 22:1263–1272.).