The mechanisms by which Cryptosporidium parvum cause persistent diarrhea and increased morbidity and mortality are poorly understood. Three groups of Haitian children <18 months old were studied: case patients, children with diarrhea not due to Cryptosporidium, and healthy control subjects. Compared with both control groups, children with acute cryptosporidiosis were more malnourished (including measures of stunting [P=.03] and general malnutrition [P=.01]), vitamin A deficient (P=.04), and less often breast-fed (P=.04). Markers of a proinflammatory immune response, interleukin (IL)-8 and tumor necrosis factor-alpha receptor I, were significantly elevated in the case population (P=.02 and P<.01, respectively), as was fecal lactoferrin (P=.01) and the T helper (Th)-2 cytokine IL-13 (P=.03). The counterregulatory cytokine IL-10 was exclusively elevated in the case population (P<.01). A Th1 cytokine response to infection was not detected. This triple cohort study demonstrates that malnourished children with acute cryptosporidiosis mount inflammatory, Th-2, and counterregulatory intestinal immune responses.