In this study we produced antigenic extracts from prototypical strains of C. neoformans (VNI-VNIV) and C. gattii (VGI-VGIV) and tested IFN-γ secretion by Elispot. Antigens from the eight Cryptococcus molecular types (VNI –VNIV and VGI - VGIV) were obtained after capsule reduction. IFN-γ secretion by Elispot method were stimulated with C. neoformans and C. gattii antigens. Peripheral blood mononuclear cells of fourteen healthy control subjects, being: five ecotourists, two mycologists, three poultry keepers, and four individuals without reports of exposure to the fungus. We observed a significant increase in IFN-γ secretion in the group of ecotourists, mycologists and bird keepers in relation to the group of individuals without reports of occupational exposures to these agents. Our results suggest the significant increase in IFN-γ secretion may be related to the continuous exposure of these groups of individuals to the fungus, as well as to the specific antigen memory immune response developed during exposure to Cryptococcus.