Surface labeling of "normal" nontumorigenic rat liver epithel cells permitted the detection of a 140,000-dalton species and of another 230,000-dalton molecule that comigrated with fibronectin, an external transformation-sensitive protein of fibroblasts. Reaction of surface-labeled normal liver epithelial cells with anti-fibronectin serum led to the selective recognition of the 230,000-dalton component, which revealed a peptide composition similar to that of the homologous fibroblasts fibronection. Similar experimental conditions with the tumorigenic liver epithelial cell counterpart revealed decreased labeling in the fibronectin region and preferential labeling in the 140,000- and 60,000-dalton regions. Arginine limitation was found to produce growth arrest in both normal and malignant liver epithelial cells, concurrent with a marked decrease in the labeling of the surface-associated fibronectin and different surface macromolecular alterations in normal and transformed cells. Mild proteolysis combined with brief neuraminidase treatment did not produce marked alterations in tumorigenic cell surface labeling but did lead to a decrease in the fibronectin of normal cells and to the increased expression of other transformation-associated changes in surface macromolecules different from fibronectin. Our results show the involvement of an arginine-regulated fibronectin and other cell surface macromolecules among the changes that occur during the conversion of normal liver epithelial cells to a malignant state.