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To examine the importance of intestinal inflammation in the diagnosis and pathogenesis of human cryptosporidiosis, stools of healthy adult volunteers before and after experimental infection were tested for fecal lactoferrin, interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Stool samples of Brazilian children with well-defined Cryptosporidium infection, with or without diarrhea, were also tested for IL-8 and TNF-α. Only one of the 14 volunteers challenged with Cryptosporidium had increased fecal lactoferrin. However, of 17 stool specimens from children with only Cryptosporidium infection from a previous study, 12 had mild to moderately elevated lactoferrin despite negative work-up for inflammatory enteritides. One of 10 adult volunteers who developed diarrhea with experimental cryptosporidiosis and three of 11 children with cryptosporidiosis and diarrhea had detectable fecal IL-8. The level of TNF-α was increased only in one of 14 volunteers and in none of the children. Although considered relatively non-inflammatory, cryptosporidiosis is often associated with mild inflammation, especially in children in an endemic area.