In this experiment, the "nu" gene was introduced into "beige" mutant mice, which are immunodeficient in NK cell activity. The resultant beige nude mice (bg/bg-nu/nu) have combined immunodeficiency in both T and NK cell activities. The level of NK cell activity in beige nude mice is slightly higher than that in beige mice, but much lower than that in nude mice. This is consistent with other studies. In order to elucidate the role of the metastatic behavior of a human tumor cell line PAa in both athymic nude mice and beige nude mice. The PAa cell line was originally established from a human lung adenocarcinoma and maintained as a solid tumor by serial s.c. passage in nude mice. During the first 18 passages in nude mice, PAa cells were found to have metastasized spontaneously to regional lymph nodes in only 4 animals, but metastases were no longer found in subsequent passages. The total incidence of metastasis in nude mice was 9% (4/44). However, when inoculated s.c. into beige nude mice, the metastatic rate of PAa cells was 43% (9/21) to the regional lymph nodes and 10% (2/21) to the lungs in two separate experiments. We conclude from the results that NK cells may play an important, if not exclusive, role in host resistance to tumor metastasis. Beige nude mice could serve as a useful in vivo model in studies of the biology and heterogeneity of human tumor metastasis.