To select human melanoma cells that are highly tumorigenic and metastatic in nude mice we have implanted fragments of a fresh human melanoma metastasis subcutaneously (s.c.) into a nude mouse. After 3 passages in nude mice, part of the xenograft was cultured and a new melanoma cell line, MV3, was established. After intravenous (i.v) inoculation of 2 × 104 MV3 cells, 95% of the nude mice (n = 20) developed lung colonies within 6 weeks. S.c. inoculation of 2 × 104 MV3 cells resulted in 95% tumor take, while 90% of the mice (n = 20) showed spontaneous metastases in the lungs within 7 weeks. Histological and immunohistological features of the original tumor of the patient were largely retained in the tumors of the mice and in the cell line in vitro. As shown by Aldan blue staining, MV3 cells contain large quantities of gly-cosaminoglycans (GAGs) and/or proteoglycanes (PGs), both in vivo and in vitro. The cells showed a marked expression of transferrin receptor, ICAM-I, EGF-receptor, and VLA-2 inte-grin. As only few human melanoma cell lines are available that frequently show metastasis in nude mice, the highly metastatic MV3 cell line represents a useful tool for studying the expression and regulation of molecules on human melanoma cells involved in the process of metastasis.