The ability of the human A375 melanoma cell line to produce experimental and spontaneous in young BALB/c nude mice was examined. Cloned lines, obtained by isolation in semisolid agar, differed significantly (4/10 cloned lines examined, P less than or equal to .005) from the parent tumor line with regard to their ability to form lung tumor nodules subsequent to iv injection. Lines established from such lung tumor nodules were more metastatic than the parent line following both iv and sc injection. These results show that the human melanoma cell line used in these studies contained cells with diverse metastatic potential and suggest that metastasis in the nude mouse results from the preferential selection of metastatic subpopulations.