The objective of this study was to determine whether changes in the ileal intraepithelial lymphocyte (TEL) phenotype and function occurred prior to development of diarrhea in Cryptosporidium parvum-infected calves. Calves were orally inoculated with 10(8) oocysts and maintained in enteric pathogen-free conditions until their use in experiments. Age-matched uninfected calves were used for comparisons. Ileal IELs were isolated and phenotyped to determine whether changes in lymphocyte population dynamics had occurred by 3 days postinoculation (PI). Ex vivo reverse transcriptase-polymerase chain reaction of messenger ribonucleic acid (mRNA) from IELs from infected calves was compared with controls to determine whether changes in cytokine expression had occurred by 3 days PI. No significant changes in lymphocyte population dynamics were documented, however, IELs isolated from 4 out of 8 infected calves, but not from 8 out of 8 control calves, expressed mRNA for interleukin-10 (IL-10). IL-10 expression by IELs was associated with the expression of a significantly larger (P < 0.001) proportion (0.75) of monoclonal antibody-defined C. parvum epitopes within infected ileal epithelium, as compared with a much smaller proportion (0.30) of epitopes with IL-10 lymphocytes. The results suggest that a temporal association exists between the expression of IL-10 by ileal IELs and the expression of C. parvum antigens in infected calf epithelium prior to development of cryptosporidiosis.