Noninvasive, toxigenic Vibrio cholerae and the invasive enteropathogens Shigella flexneri and Salmonella typhimurium stimulate secretion of fluids in rabbit ileal loops. To assess similarities in secretory mechanisms and the possible involvement of prostaglandins in secretion, indomethacin (a rapid, intense inhibitor of prostaglandin synthesis) was used. Fluid secretion mediated by S. typhimurium was completely inhibited by treatment with indomethacin. Secretions stimulated by S. flexneri, V. cholerae, and cholera toxin were reduced by 40%–60%. Indomethacin affected neither the local invasiveness of S. typhimurium or S. flexneri nor the peripheral dissemination of S. typhimurium. Therefore, indomethacin dissociated the invasive process from the secretory event. These data are consistent with the participation of prostaglandins in these enteropathogen-stimulated secretory states. This conclusion must, however, be regarded as tentative in view of other possible mechanisms of indomethacin action.