To elucidate the in vivo function of interleukin-2 (IL-2) we produced transgenic mice with either the human genomic IL-2 gene (hIL-2) or the murine metallothionein-I promoter-human IL-2 fusion gene (MThIL-2). Nine of 12 transgenic mice independently obtained showed motor ataxia (2 mice with hIL-2, and 7 mice with MThIL-2) due to the infiltration of lymphocytes into the cerebellar tissues (Katsuki et al. 1989). In addition to the ataxia shown by both groups of transgenic mice, other features were found with respect to each introduced DNA. The transgenic mice with hIL-2 suffered from alopecia. Lymphocytic infiltrates were found in the skin underlying the hairless regions as well as in the brains. On the other hand, the male transgenic mice with MThIL-2 had atrophic testes. In these male mice, sperm or cells of the later stages of spermatogenesis were depleted in the testes without any apparent signs of an immunological response. These findings suggest that the introduced human IL-2 genes may have the pleiotropic functions of inducing tissue-specific immunological responses in the brain and skin, and of having harmful effects on spermatogenesis.