Cryptococcosis is a frequently fatal disease caused by a yeast-like organism, Cryptococcus neoformans. Patients with systemic cyptococcosis generally have cryptococcal antigen in their body fluids; levels of antigen directly correlate with severity of the disease. With use of a murine model, it was documented that cell-mediated immunity is an important protective mechanism and that an epitope(s) on the mannoprotein fraction of the cryptococcal antigen present in a culture filtrate is recognized in cell-mediated immunity. Sera from mice infected with C. neoformans will induce suppressor cells that suppress cell-mediated immunity, as measured by the delayed-type hypersensitivity response, and the level of cryptococcal antigen in the serum directly correlates with the degree of suppression induced. There is no correlation with the amount of anticryptococcal antibody and the ability of the serum to induce suppression. Further, it was demonstrated that cryptococcal antigen, when injected into mice at concentrations similar to those found in human systemic cryptococcosis, induces a complex series of suppressor cells and factors that specifically suppress the delayed-type hypersensitivity response and protective immunity to cryptococci.