The B16 melanoma-derived low lung-colonizing variant B16-F1 and the high lung-colonizing variant B16-F10 retained their differential lung-colonizing abilities throughout at least 35 serial s.c. transplant generations. The majority of the cells originating from solid B16-F1 tumors had a higher density than did cells originating from solid B16-F10 tumors. Cell suspensions of unselected solid B16 melanomas contained two major subpopulations differing in their cell density. The subpopulation with the lower cell density was more efficient in lung tumor colony formation, following i.v. administration, than was the high-density subpopulation. Cloned tumors from low-density B16 cells were more efficient in lung colony formation than were cloned tumors from high-density cells.