The mechanism with which the immune system of an immunocompetent host responds to Cryptosporidium parvum infection is still poorly understood. We have therefore investigated the immune response of adult immunocompetent C57BL/6 mice at Days 6 and 10 to postinfection during a self-limiting C. parvum infection. We evaluated the immune changes at the levels of intestinal intraepithelium and lamina propria as well as mesenteric lymph nodes. At Day 6 postinfection, there was a decrease in the production of IFN-gamma, IL-5, IL-6, and IL-10 by in vitro mitogen-stimulated intraepithelial lymphocytes. Moreover, an increase in the number of gammadelta-TCR+, CD8+, and cytoplasmic IgE+ cells in intestinal lamina propria was found. Concomitantly, a significant decrease in the number of cytoplasmic IgA+ and IgG+ cells was observed. These phenotypic changes may be associated with the cytokine-producing profile (decreased IL-4, IFN-gamma, and IL-10) by lamina propria lymphocytes. At Days 6 and 10 postinfection cytoplasmic IgA+ and IgG+ cell numbers remained. Nevertheless, the production of IL-5 and IL-10 by intraepithelial lymphocytes was higher than the noninfected control values; these changes may be associated with the decreased CD4+ cell numbers. In mesenteric lymphocytes IgG and IgA production in vitro was elevated while no changes were observed in cytokine production except for a significant decrease in IL-5. In conclusion, our results demonstrate that an immunocompetent defense mechanism leading to a successful recovery from C. parvum infection involved changes of T(H1)- or T(H2)-type cytokine production as well as alterations of the lymphocyte subpopulation at mucosal-associated lymphoid tissues.