The peripheries of Lewis lung (3LL) tumor cells growing in different organs of the mouse were studied by cell electrophoresis and electron microscopic quantitation of colloid iron hydroxide (CIH) adsorption before and after incubation with neuraminidase. The results show that cells growing in the kidney after direct injection have significantly higher anodic mobilities than cells growing in the subcutaneous sites from which they were derived, or in intramuscular sites, liver or spleen. The proportional contributions of cell surface sialic acids were similar in all sites. Electron microscopy of cells reacted with CIH indicates that the increased surface charge density of the tumor cells growing in the kidney is due to the presence of increased densities of non-CIH-binding ionogenic groups. Before neuraminidase treatment, the surface distribution patterns of CIH were indistinguishably random for 3LL cells growing in all sites. After neuraminidase treatment, significantly more clustering of CIH particles was observed on 3LL cells with a history of growth in the kidney than in subcutaneous sites. The changes observed in the 3LL cells growing in the kidney were irreversible, and persisted on multiple back-transplantation to subcutaneous sites. Detailed analysis of the results shows the changes to be due to the preferential selection of a subpopulation consisting of approximately 10% of the original (subcutaneous) tumor-cell population. This evidence for an irreversible site-induced selection of a pre-existing sub-population of 3LL cells contrasts with the reversible (modulation) site-induced adaptation previously observed by us in Walker-256 cancer cells, and therefore indicates that both selective and adaptive processes can occur. Even in the case of the 3LL cells, site-specific selection is not general, since the changes were observed in tumors growing in the kidney but not in the other anatomic sites. At present we cannot comment on the relevance of these reported changes to naturally occurring metastasis.