The effect of energy deprivation (treatment with rotenone in glucose-free medium) and hyperthermia (44 degrees C) on interphase death of EL-4 thymoma, Ehrlich and HeLa carcinomas was studied in vitro. Irreversible damage accompanied by intensive blebbing with subsequent cell death (necrosis) was observed only when elevation of actin in triton-insoluble fraction occurred although some proteins became insoluble before actin. Actin-specific drugs cytochalasin B and phalloidin accelerated both actin insolubilization and cell necrosis in rotenone-treated EL-4 cells; after conditioning treatment with recovery the actin insolubilization during hyperthermia was suppressed. Ehlrich and HeLa carcinomas were much more resistant to energy deprivation and hyperthermia; this correlated with the resistance of their actin to aggregation. It is concluded that stability of actin skeleton may be determinative of tumor cell resistance to energy deprivation, hyperthermia and possibly to some other treatments.