We report the recovery of Salmonella typhi that acquired resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and gentamicin subsequent to multiple antibiotic therapy. Escherichia coli and Klebsiella pneumoniae isolates which were recovered from the same stool sample displayed identical resistance patterns. Agarose gel electrophoresis revealed that S. typhi and laboratory-derived transconjugants contained a high-molecular-weight plasmid present in the resistant intestinal bacteria.