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It has been difficult to document the postulated sequence of events that begins with the selection of drug-resistant organisms in animals fed subtherapeutic amounts of antimicrobials and ends with clinically important infections in human beings. In early 1983 we identified 18 persons in four Midwestern states who were infected with Salmonella newport that was resistant to ampicillin, carbenicillin, and tetracycline and characterized by a 38-kilobase R plasmid. Twelve of these patients had been taking penicillin derivatives for medical problems other than diarrhea in the 24 to 48 hours before the onset of salmonellosis. Eleven patients were hospitalized for salmonellosis for an average of eight days, and one had a fatal nosocomial infection. We compared plasmid profiles of all human (six-state area) and animal (United States) S. newport isolates over an 18-month period and examined selected records of meat distribution. The results indicated that the patients had been infected before they took antimicrobials, by eating hamburger originating from South Dakota beef cattle fed subtherapeutic chlortetracycline for growth promotion. This study demonstrates that antimicrobial-resistant organisms of animal origin cause serious human illness, and emphasizes the need for more prudent use of antimicrobials in both human beings and animals