The organ distribution, arrest and survival of [125I]5-iodo-2'-deoxyuridine-labeled B16 melanoma cells with low (B16-F1) or high (B16-F10) metastatic potential were studied in a variety of normal and immunosuppressed syngeneic C57BL/6 mice, allogeneic A mice, and athymic nude NIH Swiss mice and their immunocompetent littermates. In addition, the in vitro aggregation properties of these tumor cells with various host organ cells in suspension were examined. Tumor cell arrest and survival following i.v. injection occurred at significantly higher rates in normal mice than in immune-depressed animals irrespective of strain, and, two weeks later, significantly more tumor colonies were found in the normal animals. In syngeneic or allogeneic animals, B16-F10 cells were arrested, survived and formed significantly more gross pulmonary tumors than B16-F1 cells. B16-F10 cells also aggregated in vitro with purified organ cells in suspension obtained from either syngeneic or allogeneic mice at a greater rate than B16-F1 cells. These results indicate that although host properties can affect the arrest and survival of circulating tumor emboli, they do not diminish or abolish the biological differences between the high and low metastatic variant B16 lines.