The present studies are based on autopsy data showing that in upper esophageal and lower rectal carcinomas, hematogenous metastasis occurs mainly first to the lungs, and cancer cells from pulmonary metastases generate arterial metastases. In lower esophageal and upper rectal carcinomas, hematogenous metastases occur first in the liver, then in the lungs, and are further disseminated by the arterial route. The arterial metastatic patterns are different in the 2 groups. One possible explanation for these differences in pattern is that liver "residence" is associated with different metastatic behavior; this has been tested in a model system. Experiments with the transplantable colon-26 carcinoma in mice reveal that, when cancer cells from common S.C. transplant sites are grown in the liver, lungs or liver-and-lungs, and then injected into the bloodstream of fresh recipients via the left ventricle, the portal vein or the tail vein, different patterns and degrees of colonization of I I different target sites are observed. These results are consistent with the hypothesis that growth of cancers in different anatomic sites may modify the subsequent arterial metastatic patterns, due to site-induced changes occurring in cancer cell populations, which influence metastasis from metastases or so-called "cascade" processes.