In early 1983, an outbreak of illness caused by raw milk contaminated with multiple-antimicrobial-resistant Salmonella typhimurium occurred in Arizona. One of the cases involved a 72-year-old woman 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 weeks 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.