This study investigates the role of Fas in Ca²⁺-independent T cell-mediated cytotoxicity. Using thymocytes from lpr and gld mouse mutants, as well as L1210 cells transfected with Fas, the authors demonstrate that Fas is involved in the Ca²⁺-independent component of cytotoxicity mediated by nonantigen-specific in vitro activated hybridoma cells and antigen-specific in vivo raised peritoneal exudate lymphocytes. The results show that Fas transduces a cell death signal to target cells, leading to apoptosis. The study also highlights the importance of Fas in both developmental and functional cell death within the immune system. Additionally, the authors provide evidence that Fas-based mechanisms may account for a significant portion of specific T cell-mediated cytotoxicity, particularly its Ca²⁺-independent component.This study investigates the role of Fas in Ca²⁺-independent T cell-mediated cytotoxicity. Using thymocytes from lpr and gld mouse mutants, as well as L1210 cells transfected with Fas, the authors demonstrate that Fas is involved in the Ca²⁺-independent component of cytotoxicity mediated by nonantigen-specific in vitro activated hybridoma cells and antigen-specific in vivo raised peritoneal exudate lymphocytes. The results show that Fas transduces a cell death signal to target cells, leading to apoptosis. The study also highlights the importance of Fas in both developmental and functional cell death within the immune system. Additionally, the authors provide evidence that Fas-based mechanisms may account for a significant portion of specific T cell-mediated cytotoxicity, particularly its Ca²⁺-independent component.