Two human melanoma lines with low (HT168) and high (HT168-MI) liver metastatic capacity in immunosuppressed mice were selected in vivo from the A2058 cell line. After i.v. injection of the 2 tumor lines there was no significant difference either in the number of lung colonies or in the frequency and tissue distribution of extrapulmonary tumor deposits. These findings suggest that the selection in the spleen-liver system did not result in an overall increase in the metastatic potential of the melanoma cells, but rather that it represented an organ-preferential selection. The HT168-MI cells did not acquire an increased growth rate in vitro or in vivo, suggesting that other phenotypic alterations are responsible for the enhanced metastatic capacity. The 2 tumor lines were characterized by similar expression of HLA-A,B,C, transferrin receptor and melanoma-associated proteoglycan antigen. HT168 contained more NGF receptor, while HLA-DR appeared only on HT168-MI cells. This human metastasis model could be useful in studying the mechanisms of liver metastasis formation, as well as in revealing possible new targets of antimetastatic therapy.