A studies of cytotoxic cells in athymic nude mice demonstrate higher cytotoxic activity of NK cells and macrophages than in their euthymic counterparts. The higher level of endogenous cytotoxic activity can be considered as complementary to the deficiency or lack of thymus dependent T lymphocytes and their functions. However, with increased age of mice some T lymphocytes and their functions can be demonstrated. By stimulation of splenocytes and lymph node cells in vitro with IL-2 or anti CD3 antibody cytotoxic activity towards P-815 (NK resistant, LAK sensitive) target cells can be generated. There exist data, which indicate that the cytotoxic activity is exerted by extrathymic pre-T lymphocytes with TcR gamma delta antigenic phenotype. The differences in transplantability of human tumors in athymic nude mice cannot be explained by defect in antigen recognition and in immune response of athymic nude mice, recipients of the xenografted material. The biological relevance in vivo of high endogenous cytotoxicity of NK cells observed in many strains of athymic nude mice remains obscure. The availability of new immunodeficient mouse models, e.g. scid mice deficient in B and T lymphocytes and with low level of NK cells, in which not only xenografted human tumor grow but human lymphoid cell can be transplanted as well, opens new and broader experimental possibilities, in which new preclinical immunotherapeutical approaches can be applied.