A 78-yr-old woman with a history of hypochlorhydria was found to have pseudomembranous colitis due to Clostridium difficile. She had not received previous antimicrobial therapy. Her onset of disease followed ingestion of possibly contaminated canned salmon, suggesting possible oral transmission of disease. We assessed the possibility of ingested Clostridium difficile organisms or cytotoxin surviving passage through the upper gastrointestinal tract. Normal gastric juice, hypochlorhydric gastric juice, and duodenal secretions were obtained from volunteers and tested for their ability to kill Clostridium difficile organisms or inactivate toxin. These in vitro studies indicated that the primary upper gastrointestinal barriers for ingested Clostridium difficile and cytotoxin were pH-dependent. We suggest that oral transmission of disease due to Clostridium difficile may occur in hypochlorhydric patients.