Mice with severe combined immunodeficiency (scid) provide an excellent model for studying interactions between human tumor cells and effector cells of the immune system. Because these animals lack functional B and T lymphocytes, they can accept human tumor xenografts and transfer of human effector cells. Here, we determined the ability of a human melanoma-specific, cytotoxic T-cell line (CTL) in suppressing the growth of spontaneously metastasizing human melanoma cells M24 met (HLA-A11, A33) in scid mice. This CTL line was highly cytotoxic and restricted by HLA-A11 against M24 met melanoma cells in vitro but poorly cytotoxic when tested against a human melanoma cell line that did not express HLA-A11. In order to evaluate the efficacy of this CTL line against M24 met melanoma cells in vivo, randomized groups of animals were given injections of either RPMI culture medium, interleukin 2 (IL-2), CTLs, or CTLs + IL-2. IL-2, per se, did not significantly reduce tumor metastases; however, injection of melanoma-specific, HLA-A11 restricted CTLs into scid mice, 1 day postexcision of the previously induced primary tumor, markedly reduced the number of metastatic foci in the lung and decreased metastatic involvement in lymph nodes. The combination of these CTLs with IL-2 proved even more effective, since almost all lung metastases were eradicated and metastatic involvement in both axillary and inguinal lymph nodes was substantially reduced. Our results indicate that these human CTLs maintain their ability for specific killing of metastasizing melanoma cells in scid mice. Our data suggest that reconstitution of scid mice with a specific group of effector cells (step-wise scid/hu) may be helpful for in vivo evaluation of potentially useful cancer immunotherapy modalities.