In July 1974, mebendazole was reported to be effective against the larval stage of Echinococcus granulosus in experimentally infected mice. A clinical trial of mebendazole was initiated in December 1974 in 4 patients with far advanced, nonresectable lesions caused by Echinococcus multilocularis. A daily dose of 40 mg of the drug per kg of body weight was administered to the 4 patients for more than 3 years. No evidence of toxicity or adverse reactions has been observed. Detectable plasma mebendazole concentrations were achieved with high-dose mebendazole therapy. Serum concentrations of IgE increased and decreased early in therapy. There was no evidence that the larval cestode was killed. The metastatic lesions appeared to be stabilized or diminished, and over-all clinical results were encouraging. Progressively enlarging thoracic metastases in 2 patients regressed during therapy, and symptomatic improvement was observed in all 4 patients. Mebendazole, a highly effective antihelmintic in enteric infections, is poorly absorbed by the gastrointestinal tract. Resulting low serum concentrations limit treatment of the massive, scirrhous lesions characteristic of E. multilocularis infections. Nevertheless, encouraging clinical responses observed with mebendazole therapy suggest that a more soluble form of this or a related drug might prove highly effective in the medical management of hydatid disease in humans.