Cryptosporidiosis is an important cause of diarrhea worldwide. In normal hosts, infection is self-limited and associated with seroconversion and partial immunity to reinfection. Immunity is associated with interferon gamma (IFN-γ) production. Cryptosporidium surface proteins gp15 and gp40 are among the immunodominant proteins in terms of antibody responses. We asked the question of whether these antigens also stimulate production of IFN-γ in patients who have serologic evidence of prior infection. Whole blood from seropositive donors was stimulated with recombinant gp15 and gp 40 from Cryptosporidium hominis and Cryptosporidium parvum or His-tag controls. C hominis gp15 stimulated increased production of IFN-γ. By contrast, there was no significant increase after stimulation with C parvum gp15 or either gp40 preparation. IFN-γ production in response to C hominis gp15 was noted in both CD4+ and CD8+ cells. This highlights the potential for C hominis gp15 as a vaccine candidate for human cryptosporidiosis. Copyright © 2007 by The American Society of Tropical Medicine and Hygiene.