The behavior pattern of tumor cells in the development of hematogenous liver metastasis by Yoshida sarcoma and two strains of rat ascites hepatoma, AH7974F and AH13, in Donryu strain rats was investigated by electron microscopy. Tumor cells of every strain in liver sinusoids stretched their cytoplasmic protrusions toward the vascular wall and were actually in contact with the endothelial cells with their tips to form various types of junction-like structures. The most distinct one was characterized by parallel and straight arrangement of the opposing cell membranes across a gap of about 100 A. The endothelial discontinuity was easily produced by the projection of cytoplasmic processes and the compression of tumor cells. Through the endothelial defect, tumor cells of Yoshida sarcoma and AH13 migrated locomotively into the dilated spaces of Disse or directly toward the hepatic cells, while AH7974F cells were frequently covered by elongated endothelial cytoplasm. Destruction of the hepatic cells by AH7974F and AH13 cells was found to begin with the insertion of their cytoplasmic processes into the coated vesicles in the hepatic cells. From these investigations, the particular interaction between tumor and normal cells seems to play an important role in the development of liver metastasis by these tumors.