Immunohistochemical studies on the main entrance-route of CA19-9 into the peripheral venous blood of gastric cancer patients. Correlation with CA19-9 levels in peripheral and portal blood. The correlation between CA19-9 levels of portal and peripheral venous blood, and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases. Immunohistochemically, CA19-9 was found in 33 (62.5%) of 53 primary lesions. The antigen was found in the cancer cells of invasive lymphatics and node metastases of every CA19-9 localized cancer, although the cancer cells in veins showed little or no CA19-9. There was little or no antigen in the cancer cells in veins, lymphatics, or metastases of 20 CA19-9 nonlocalized primary lesions. Patients with CA19-9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood. CA19-9 levels of portal blood (mean, 76.4 U/ml; positive rate, 33.3%) were not different from those of peripheral blood (mean, 91.5 U/ml; positive rate, 33.3%). Additionally, the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases, and every patient without the invasion showed no elevation of the antigen. These results suggest that production of the antigen in cancer cells may be a premise of CA19-9 elevation in peripheral blood and that CA19-9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics, but not by the hematogenous portal system. 