We treated female Swiss Webster mice with heavy, long standing infections of Echinococcus granulosus with mebendazole, 50 mg/kg body weight daily for 10 days and bithionol, 70 mg/kg every other day for four doses. Necropsy performed 6 weeks after completion of therapy showed no gross or histologic differences between untreated controls and bithionol-treated mice or their cysts. Mebendazole-treated mice had a significant decrease in the total number of cysts (15 vs. 100), with many of those present being ruptured. Electron microscopy of intact, mebendazole-treated cysts revealed a marked increase in vacuolization and disarray of the distal cytoplasm, dilated and degenerating microtubules, increase in the size and number of lysosomes, a decrease in the number of normal appearing golgi, and increased density of mitochondria. Several mice died shortly after the termination of mebendazole therapy, all with ruptured cysts. Due to the large volume of the cysts, the presumed cause of death was acute volume overload, but toxic or anaphylactic reactions could not be excluded. We suggest that any proposed chemotherapy of humans with hydatid disease be done cautiously, with careful monitoring.