A 43-year-old woman continued to carry Salmonella thompsoni in her stool despite large oral doses of ampicillin sodium. The organisms were sensitive to ampicillin but the stool was found to contain large quantities of penicillinase which inactivated the antibiotic. Treatment with ampicillin plus cephaloglycin dihydrate resulted in negative stool cultures, probably because cephaloglycin bound penicillinase. Thus, destruction of ampicillin by penicillinase elaborated by enteric organisms was the probable mechanism for persistence of salmonellae in this patient's stools.