Immune reactions to cysticercosis have been extensively studied in mice. The lack of significant lymphocyte infiltration into the livers of infected mice and the obvious role of antibodies in rejection has led to the general conclusion that cellular reactions do not play a role in protection against this disease. In contrast, the present study examining the immune response to cestode infections in a large animal model (sheep) revealed the presence of a massive and highly organized cellular infiltration in the livers after a secondary Taenia hydatigena infection. The majority of the infiltrating lymphocytes were of the CD4+ phenotype with much fewer CD8+ cells present. While most gamma delta-TCR+ cells in peripheral blood are SBU-T19+, the majority of gamma delta-TCR+ lymphocytes in the liver lesions are SBU-T19- suggesting selective migration of these cells into the lesions. In contrast to the diffuse distribution of T cells in the lesions, B cells were present as distinct aggregates. In primary T. hydatigena infections, host class I and class II MHC antigens were shown, for the first time in cestode infections, to be absorbed onto the surface of the metacestode bladderwall indicating their possible involvement in parasite survival. No immune reactions were observed close to the parasite although lymphocytes and eosinophils were infiltrating the adjacent portal tract areas. Most lymphocytes in both primary and secondary infections were positive for MHC class II antigens suggesting selective recruitment of activated cells to the site of infection. Significant changes in relative and absolute numbers of lymphocyte subpopulations were also observed in the draining hepatic lymph nodes dominated by a massive increase of B cells. In contrast, at the peak of local cellular infiltration, no changes in lymphocyte subpopulations were observed in peripheral blood showing the limited usefulness of this compartment in studying cellular changes in localized infections. The vigorous cellular response observed in the livers of sheep contrasts sharply with the lack of lymphocyte infiltration reported in mice indicating that small animal models may not be appropriate to study cellular responses to cysticercosis in large animals and man.