Susceptibility or resistance to infection with Cryptosporidium parvum correlates with the ability of mice to produce characteristic panels of cytokines in response to infection. Both adult healing and nonhealing mouse models of cryptosporidiosis were used to study the cell-mediated immune response during the course of C. parvum infection. Mesenteric lymph node (MLN) lymphocytes from both mouse models were proliferated after ex vivo re-stimulation with C. parvum sporozoite antigen. Study of the cytokine profile from the supernatant of proliferated MLN cells revealed that healing mice produced greater levels of Th1 (IFN-gamma and IL-2) and moderate amounts of Th2 (IL-4, IL-5, IL-6, and IL-10) cytokines throughout the course of infection. Whereas, MLN cells from nonhealing mice produced no IFN-gamma, low levels of IL-2 and IL-4, and higher levels of IL-5, IL-6, and IL-10 cytokines. These results suggest that the capacity to produce both Th1 and Th2 cytokines, rather than the presence of Th2 cytokines alone, determines the effective immune response against C. parvum infection.