Shiga toxin-producing Escherchia coli (STEC) comprises a group of attaching and effacing (A/E) enteric pathogens of animals and humans. Natural and experimental infection of calves with STEC may result in acute enteritis or subclinical infection, depending on serotype-and host-specific factors. To quantify intestinal secretory and inflammatory responses to STEC in the bovine intestine, serotypes that are associated with human disease (O103:H2 and O157:H7) were introduced into ligated mid-ileal loops in gnotobiotic and conventional calves, and fluid accumulation and recruitment of radiolabeled neutrophils were measured after 12 h. STEC serotype O103:H2, but not serotype O157:H7, elicited strong enteropathogenic responses. To determine if the inflammatory response to STEC O103:H2 in calves requires Shiga toxin 1 or intimate bacterial attachment to the intestinal epithelium, defined mutations were made in the stx1, eae, and tir genes. Our data indicate that some STEC induce intestinal inflammatory responses in calves by a mechanism that is independent of A/E-lesion formation, intimin, or Shiga toxin 1. This may have implications for strategies to reduce STEC carriage in cattle.Shiga toxin-producing Escherichia coli (STEC) comprises an emerging group of zoonotic enteric pathogens (41). In humans, STEC infections result in bloody or nonbloody diarrhea, which may be complicated by hemorrhagic colitis and severe renal and neurological sequelae, including hemolytic uremic syndrome (HUS) (45, 55). The pathogenesis of HUS is believed to involve the translocation of Shiga toxin (Stx1 and/or Stx2; also called verocytotoxins), produced by STEC in the intestinal lumen, to systemic sites, where they cause microvascular endothelial cell damage, fibrin-platelet thrombus formation, and thrombocytopenia (45).Cattle are an important reservoir of STEC (25), and human infections are frequently associated with the consumption of contaminated beef and dairy products (26). Severe cases of infection of susceptible calves with bovine virulent STEC strains may result in atrophy of the villi, epithelial cell damage, diffuse infiltration of neutrophils into the lamina propria and intestinal lumen, and the formation of a pseudomembrane containing blood, fibrin, cellular debris, and neutrophils (29,46). A similar histopathology occurs in some cases of STECassociated hemorrhagic colitis in humans (27,55). An understanding of the induction of intestinal inflammatory responses to STEC is important in the development of strategies to reduce the prevalence of STEC in cattle. By implication, such strategies may lower the incidence of human STEC infections.Infection of the gastrointestinal tracts of conventional cattle and 5-day-old gnotobiotic calves by STEC serotype O157:H7 is asymptomatic (5, 63). However, E. coli O157:H7 is frequently associated with human disease, and the molecular basis of STEC serotype host specificity is unknown. Infection of neonatal colostrum-deprived calves with E. coli O157:H7 may result in enterocolitis similar to that s...