Neurocysticercosis, caused by Taenia solium is arguably the most common parasitic disease of the central nervous system. In taeniid infections of nonhuman mammals, there is strong evidence of immunity in the intermediate host to the invasive larvae (oncospheres). This immunity, which is mediated by antibody and complement, has been exploited to develop vaccines that effectively prevent infection. To examine the immune response in humans, T. solium eggs were hatched and activated in vitro. Activated oncospheres were incubated with heat-inactivated sera from patients with neurocysticercosis with or without complement (guinea pig serum). Controls included oncospheres plus complement alone, normal human serum alone, normal serum with complement, or buffer alone. Serum from infected patients, especially with complement, markedly reduced oncosphere mobility and led to disappearance of secretory vesicles and loss of membrane integrity. Viability as assessed by staining with dimethyl-thiazolyl-diphenyl-tetrazolium was reduced from 92.5% in controls to 61.5% with immune serum and 38.8% with immune serum and complement (P < 0.01). Preliminary western blot analysis showed antigens at 22, 64, and 70 kDa recognized by all 3 sera, but not by control sera. These data suggest that sera from patients with cysticercosis can kill oncospheres in vitro and may be used to identify protective antigens.