We conducted laboratory-based surveillance and a case-control study to characterize the epidemiology of bloody diarrhea in rural Western Kenya. From May 1997 through April 2001, we collected stool from 451 persons with bloody diarrhea presenting to four rural clinics. Cultures of 231 (51%) specimens yielded 247 bacterial pathogens: 198 Shigella (97 S. flexneri, 41 S. dysenteriae type 1, 39 S. dysenteriae type non-1, 13 S. boydii, 8 S. sonnei), 33 Campylobacter, 15 non-typhoidal Salmonella, and 1 Vibrio cholerae O1. More than 90% of the isolates (excluding Campylobacter) were resistant to trimethoprim-sulfamethoxazole and tetracycline, and more than 80% were resistant to ampicillin. Most (74%) ill persons received medication to which their isolate was resistant. Drinking Lake Victoria water and sharing latrines between multiple households increased risk of bloody diarrhea. Washing hands after defecating was protective. Providing safe drinking water and more latrines, and promoting hand washing could reduce the burden of illness from bloody diarrhea while limiting injudicious antimicrobial use.