Resistance to and control of Cryptosporidium parvum infection in mice in the absence of adaptive immunity appears to be gamma interferon (IFN-gamma) dependent. Using an IFN-gamma-neutralizing antibody in a murine model, we demonstrated increased susceptibility to infection within 24 h. We correlated this early resistance and control with increased mucosal expression of IFN-gamma and demonstrate that CD8+ T-cell receptor alphabeta intestinal intraepithelial lymphocytes express and secrete this cytokine shortly after infection. The rapid kinetics of IFN-gamma expression and secretion by naive CD8+ T cells in response to a protozoan pathogen have not previously been demonstrated.