Histoplasmosis is an important respiratory infection and the mechanism of immunity to histoplasmosis is not clearly defined. We have recently shown that the immunity elicited by sublethal infection or by immunization with ribosomal preparations from yeast cells of Histoplasma capsulatum is mediated by thymus-derived (T) lymphocytes. The overall objective of the proposed research is to study the mechanism of acquired immunity to experimental histoplasmosis using mice immunized by sublethal infection with live yeast cells of H. capsulatum. The proposed research involveds the study of the relative roles of different lymphocytes and macrophages in immunity to histoplasmosis. The experimental procedures will include separation and characterization of lymphocytes, adoptive transfer of immunity, antibody-dependent cell-mediated cytotoxicity, assessment of activation of alveolar and peritoneal macrophages, use of silica to block macrophage activity and poly-w-vinylpyridine N-oxide to abrogate macrophage blocking. In addition, experiments have been designed to study the relationship between protective immunity and delayed-hypersensitivity. It is anticipated that an understanding of the mechanism of anti-histoplasma immunity in the proposed experimental model would provide valuable information for the development of host-directed immunotherapy for histoplasmosis.