The cell-mediated immune responses are of primary importance in immunity to histoplasmosis, but the relative contribution of macrophages and different lymphocyte subpopulations in the expression of anti-Histoplasma immunity is not clearly defined. Our aim in the proposed research is to study the natural and immune cell-mediated cytotoxicity to yeast cells of H. capsulatum using mice immunized with ribosomes and by sublethal infection with yeast cells of the organism. The proposed research involves the study of the relative roles of different lymphocyte subpopulations and macrophages in the cytotoxic activity to H. capsulatum. The experimental procedures will include characterization of macrophage and lymphocyte subpopulations, natural cytotoxicity, antibody-dependent and T cell-mediated cytotoxicity to Histoplasma. The interactions between lymphocytes, macrophages and Histoplasma will also be studied by scanning and transmission electron microscopy in an attempt to determine any alterations in the morphological characteristics of these cells. It is anticipated that the information obtained from the proposed study will enhance our understanding of the mechanism of immunity to histoplasmosis.