Cytotoxic T lymphocytes (CTL) induce a cytolytic process in target cells which, like the glucocorticoid-mediated cytolysis of immature thymocytes, effects a rapid and characteristic degradation of chromosomal DNA. I have explored the possibility that these two lethal processes share a common pathway by studying the susceptibility of glucocorticoid-resistant mutants to CTL-mediated killing. Here, I report that an unusual thymoma mutant, which has normal hormone receptor activity, is resistant to both glucocorticoids and CTL. The failure to be killed by CTL is not due to an inability of this 'deathless' mutant to be recognized. Further, a single-step reversion can restore sensitivity to both glucocorticoids and CTL. The genetic locus thus identified may reveal one element of an endogenous suicide pathway that can be triggered by different effectors. Unlike complement-mediated lysis, the processes of glucocorticoid- and CTL-mediated cytolysis seem to require that target cells be active in their own death.