We investigated the effects of amiloride and its derivative MH-12-43 on the thermosensitivity of adriamycin-resistant cells. Effects of hyperthermia at 42 degrees C were enhanced by 0.5 mM amiloride and 0.05 mM MH-12-43, which resulted in no decrease in survival rate by the treatment at 37 degrees C for 120 min. Therefore, the combination of hyperthermia and amiloride derivatives was effective in the adriamycin-resistant cells as well as wild type cells. Further, since the survival rates by the treatment with 0.05 mM MH-12-43 were markedly lower than those with 0.5 mM amiloride from hyperthermia at 42 degrees C, MH-12-43 might be more effective than amiloride.