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 2 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.