Cryptosporidium parvum is an intracellular protozoan parasite of the mammalian intestine. In rats, C. parvum infection is age related; infants are susceptible while adults are resistant. The transition from susceptibility to resistance usually takes place as the infant rats approach the age of weaning. In the present study, infant rats were orally inoculated with a preparation of intestinal scrapings taken from adult rats or cows. The infant rats received the scrapings from days 3 to 14 of age, and were inoculated with C. parvum oocysts at 9 days of age and killed at 15 days of age. Both ileal tissue and fecal samples were examined for the presence of C. parvum. Scores for severity of infection in the ileum, as well as the degree of oocyst shedding in the feces, were both significantly lower in the groups that received the intestinal scrapings. This suggests the presence of a protective factor in the preparation that could be transferred from adults to infants. Boiling the intestinal scrapings caused a loss in the ability to protect against infection indicating that the active component was heat labile. Infant rats that received irradiated adult intestinal scrapings were also significantly less infected than the control group, indicating that protection was not dependent on the presence of live bacteria. Attempts were made to further isolate and purify the active component(s) of the intestinal scrapings through differential centrifugation, ammonium sulfate precipitation and DEAE chromatography. The biologic activity was tested by the ability of the various isolated fractions from the purification steps to protect infant rats from C. parvum infection. The activity was found to be associated with the extrinsic membrane protein fraction of the intestinal scrapings with a molecular mass greater than 10 kDa. Treating the fraction with Proteinase K caused a significant loss in the ability of the fraction to protect infant rats from infection. This indicated that the active fraction contained protein essential to its activity. The activity was found to be in the extrinsic membrane protein fraction precipitated by 40% ammonium sulfate. Separation by ion exchange resulted in four fractions, two of which were able to reduce C. parvum infection in infant rats;Identification of the protective component in adult intestinal scrapings may contribute to understanding mechanisms of resistance to C. parvum infection.