In early 1983, an outbreak of illness caused by raw milk contaminated with multiple-antimicrobial-resistant S. typhimurium occurred in Arizona [USA]. One of the cases involved a 72-yr-old women who died with Salmonella enteritis and sepsis that had not responded to treatment with chloramphenicol. The S. typhimurium isolates from this patient, from other ill persons, and from raw milk were resistant to ampicillin, chloramphenicol, kanamycin sulfate, streptomycin, sulfonamide, and tetracycline. These resistances were mediated by a 105-megadalton R plasmid. During the epidemic period, 43% of the S. typhimurium isolates submitted to the Arizona Department of Health Services were resistant to chloramphenicol, and 80% of these possessed the same plasmid resistance. Although there was evidence of spread of the S. typhimurium in the community, there was no evidence of spread of this Salmonella R plasmid to the normal flora of patients or their family members a median of 14 wk after the infection. This outbreak demonstrates the ability of drug-resistant Salmonella to spread from the animal to the human reservoir and, in a suitable host, produce a fatal infection.