Growth of B16 melanoma metastatic variants with 2.5 micrograms/ml of bromodeoxyuridine (BrdU) decreases cell detachment from the substratum, as measured by resistance to release by trypsin-EDTA treatment. Using an antiserum to intact melanoma cells and metabolic labelling of melanoma metastatic variants with 3H-glucosamine and subsequent electrophoretic analysis, we are now able to show that: (1) differential solubilization and immune precipitation permit the identification of hydrophilic glycoproteins of about 140 kD and 110 kD in melanoma cells with low colonizing ability; (2) the effects of BrdU on B16 melanoma appear to be exerted differentially on cells with differing metastatic behavior, since only poorly invasive melanoma cells show a stimulating effect of BrdU on the expression of the hydrophilic 140 kD glycoproteins; (3) cells with increased lung colonizing ability reveal hydrophobic 140 and 110 kD glycoprotein species with increased susceptibility to mild protease treatment, as compared with the corresponding components from poorly invasive cells. The possible relationship of the 140-110 kD glycoproteins to B16 melanoma biological behavior and cell-substratum interactions is suggested by the fact that such components undergo significant changes in cells with differing invasive behavior and detachment properties.