We examined 141 Salmonella typhi strains of known phage type isolated during ongoing epidemiologic studies in Santiago, Chile, and Lima, Peru. Plasmids were present in 12 (17%) of 70 S. typhi isolates from Santiago and 5 (7%) of 71 isolates from Lima; these plasmids were not associated with antimicrobial resistance. Identical 21 kilobase (kb) plasmids (as defined by restriction endonuclease digest pattern) were present in 13 of the 17 plasmid-containing isolates. Virtually identical digest patterns were identified when chromosomal DNA of selected strains from Santiago, Lima, and the United States was extracted and then digested with restriction endonucleases. The similarities among plasmids and chromosomal digest patterns emphasize the homogeneity and possible clonal origin of S. typhi isolates; these data also suggest that there is only a limited role for plasmid and chromosomal analysis as a substitute for phage typing in epidemiologic studies.