Serine protease genes (C11, B10 and HF) derived from activated cytolytic T lymphocytes have been shown to be important in CTL-mediated cytotoxicity. In this study, we examined the expression of these genes in fresh natural killer (NK) cells from severe combined immunodeficiency (SCID) and athymic nude mice, as well as in T-cell lines with NK activity. All of these serine protease genes were expressed in NK cells freshly isolated from SCID and athymic nude mice. In addition, all lines showed similar strong levels of expression of C11 and B10 genes, but not the HF gene. However, levels of expression in the T-cell lines did not correlate with levels of NK-like cytotoxicity. These results suggest that C11, B10 and HF serine protease genes are necessary but not sufficient for NK-like cytotoxicity.