When humans serve as inadvertent intermediate hosts for Echinococcus multilocularis, disease (alveolar echinococcosis [AE]) may result from the expanding parasite metacestode in visceral organs, mostly in the liver. Benzimidazole carbamate derivatives such as mebendazole and albendazole are used for chemotherapeutic treatment of AE. However, these treatments are, in most cases, parasitistatic rather than parasiticidal. As treatment is discontinued, a recurrence of parasite growth has been observed in many AE patients with nonradical resections. The only curative treatment for AE is radical surgical resection of the parasite tissue and support by chemotherapy. As there is a need for new treatment options for AE, the in vitro efficacy of nitazoxanide (NTZ), a broad-spectrum drug used against intestinal parasites and bacteria, was investigated. We showed that in vitro treatment of E. multilocularis metacestodes with NTZ induced high levels of alkaline phosphatase activity in the medium. Concurrently, distinct morphological and ultrastructural alterations were detected. Most significantly, two distinct types of alterations were observed as soon as after 3 h of NTZ treatment. At first, the drug induced a peripheral output of membranous vesicles from the tegumental membrane into the laminated layer. Simultaneously, germinal layer-associated undifferentiated cells produced large vacuoles filled with lipid-like and often electron-dense membranous segments. Other alterations were observed at later time points, including vacuolization of the germinal layer, accumulation of lipid droplets, and lastly, loss of microtriches and separation of the laminated and germinal layers. The pattern of damage induced by NTZ was different from the alterations earlier observed in albendazole sulfoxide-treated vesicles. The nonviability of NTZ-treated metacestodes was confirmed through bioassay, i.e., inoculation of treated and untreated parasites into mice. These experiments demonstrate the in vitro parasiticidal effect of NTZ on E. multilocularis metacestodes.Alveolar echinococcosis (AE) is caused by the metacestode (larval) stage of Echinococcus multilocularis and is a rare but life-threatening disease. The reported incidence rate per year is 0.02 to 1.4/100,000 population (7,8). The geographical distribution of E. multilocularis is confined to Palearctic regions of the northern hemisphere extending from central Europe throughout northern and central Eurasia to the Far East, including Japan, and to North America (Alaska, Canada, and the northern and central United States). In central Europe, recent surveys on E. multilocularis infection in red foxes have revealed that the parasite has a much wider geographical distribution than previously reported. The prevalences of E. multilocularis in red foxes differ extensively within and between areas of endemicity, from about 1% to over 60% (5,8).The adult worm exists as an enteric parasite in the fox and a few other carnivores, such as the wolf, cat, and dog. Parasite eggs are shed into the envi...