The occurrence of a foodborne outbreak of Salmonella drypool, an uncommon serotype, led to the recognition of hospital-acquired cases occurring over a 5-year period. In late 1981, a catered luncheon resulted in an epidemic of S. drypool, and in retrospect, cases were found to have been occurring in hospital patients from 1977 until 1981. Over the next 4 months, patients, employees, and 50% of the kitchen workers became infected, despite repeated culture surveys of the staff and removal of all infected workers. Food and environmental cultures failed to reveal the source of infection, but infected workers were observed to have multiple negative cultures over several months and then to become positive again. Closing of the kitchen for 2 weeks failed to stop the epidemic. Finally, all kitchen employees, both infected and uninfected, were treated with trimethoprim-sulfamethoxazole for 2 weeks. After treatment, no new kitchen workers became infected, although two workers who had had positive cultures earlier in the epidemic began to excrete S. drypool again, and the epidemic ended.