The cytolytic action of glucocorticoids and of agents increasing cyclic AMP were studied in corticosensitive and corticoresistant mouse thymocyte populations. Studies performed in corticosensitive cells showed that prostaglandin E2, isoproterenol and dibutyryl cyclic AMP were also able to induce cell lysis. Moreover, isoproterenol and dexamethasone exerted additive cytolytic effects. In contrast, cells isolated from hydrocortisone-treated animals were only moderately sensitive to the cytotoxic action of dexamethasone in vitro and insensitive to the action of prostaglandin E2, isoproterenol and dibutyryl cyclic AMP. Finally, we showed that the cytolytic action of dexamethasone, but also that of prostaglandin E2 and isoproterenol, could be blocked in the presence of cycloheximide, an inhibitor of protein synthesis, thus suggesting that glucocorticoids and agents increasing cyclic AMP control the synthesis of some proteins involved in the triggering of cell lysis.