The aim of this research program is to investigate mechanisms of protective immunity and immunopathology in schistosomiasis with the ultimate goal of immunologic intervention. Progress was achieved in the following areas during the year: 1) Role of IL-10 and IL-4 in the regulation of immunopathology. Single and double cytokine-deficient animals were used to study the regulatory functions of IL-10 and IL-4 in the development of the T helper response to schistosome eggs and granulomatous inflammation. 2) Chemokine expression patterns during granuloma formation and the role of MIP-1alpha receptors. Chemokine expression was measured in the lungs of mice undergoing polarized granulomatous responses and the function of receptors for the chemokine MIP-1alpha analyzed in mice genetically deficient for CCR1. 3) Role of the humoral response in down-regulation of egg-pathology. Mice deficient in either Fcepsilon or Fcgamma receptors developed larger egg granulomas with no significant alteration in the T cell response to egg antigens. These findings support previous evidence from studies in B cell deficient mice indicating an important down-regulatory role for humoral Ab in schistosome egg pathology. 4) Elucidation of developmental changes in larval susceptibility to nitric oxide (NO) mediated killing. Lung-stage schistosomula were shown to lose their resistance to NO mediated killing by 2.5 weeks of age, a change which correlated with stage-specific metabolic differences. These results support the concept that the Th1 response may act principally against older schistosome larvae.