Complement has been shown to lyse protoscoleces of Echinococcus granulosus, but products from this parasite are able to consume complement, and this has been proposed as an evasion mechanism. The murine secondary hydatidosis model, with intraperitoneal inoculation, is used in this work to assess the occurrence in vivo of complement consumption by the parasite as well as the role of complement during the establishment of infection. Although the measurement of systemic levels of C3 activation, total C3, and hemolytic complement in challenged mice yielded no evidence of complement consumption, the relevance of local consumption at the site of infection cannot be ruled out. The role of complement during establishment of infection was assessed by comparing parasite burdens in normal and complement-depleted mice. Complement depletion by treatment with cobra venom factor caused a 79% reduction in cyst numbers (P < 0.05). Possible explanations of this unexpected result are discussed. The results presented suggest that lysis or opsonization by host complement are not effective against the establishing parasite in this model. They also indicate the significance of complement activation by the parasite needs to be studied at a local level.