Several in vitro properties of two variant cell lines of the B16 melanoma (B16-F10 and B16-BL6) with markedly different spontaneous metastatic behavior were examined. The two cell lines were compared with regard to their in vitro growth rate, ability to migrate, ability to adhere to a variety of substrata, detachment rates, production of plasminogen activator, and cell surface proteins as determined by lactoperoxidase-catalyzed iodination. Growth rates in vitro, attachment rates, and qualitative patterns of cell surface proteins were almost identical. B16-F10 cells (the less spontaneously metastatic line) produced greater amounts of plasminogen activator, were more motile in vitro, and detached more readily from plastic than the more invasive B16-BL6 cells. The study of tumor cell variants, selected for different biologic behavior, is a valuable approach to the elucidation of those mechanisms responsible for their malignant activity.