The cellular immune response may be the principal mechanism of defense against infection with Histoplasma capsulatum. Subsequently, regulation of cell-mediated immunity could be fundamental to the outcome of disease. Suppressive phenomena-present in the host before infection or brought about by fungal components-would explain the various courses of infection. The fact that high titers of antibodies are associated with a poor cellular response suggests that antibodies may have a role as "regulatory molecules" in histoplasmosis. Antibodies may modulate the expression of the cellular response either by direct inhibition or by activation of the suppressor cell population, thereby interfering with the infectious process.