The cytokine interferon-gamma (IFN-gamma), initiates both cell cycle arrest and cell death in certain cell lines. Through a novel strategy of cell transfection with episomal vectors expressing antisense cDNAs, Deiss et al. have demonstrated that it is possible to isolate genes that are required for the initiation of cell death by the cytokine IFN-gamma. This approach, referred to as TKO, for Technical Knock Out, has identified several genes whose activity appears to be essential for the induction of apoptosis by IFN-gamma in HeLa cells. Interestingly, these genes appear to mediate IFN-gamma-induced apoptosis in HeLa cells, but their inhibition by antisense does not ameliorate the antiproliferative effects of IFN-gamma in these cells. The clever strategy employed by these authors holds promise for others who wish to isolate genes required for other differentiative processes in cultured cell lines.