A case of typhoid fever caused by a multiply antibiotic resistant strain of Salmonella typhi is reported. The S. typhi strain was resistant to ampicillin, chloramphenicol and sulphamethoxazole-trimethoprim. Treatment with cefotaxime, resulted in a clinical and bacteriological cure, but the infection relapsed within a month after completion of therapy. It resolved completely with oral ciprofloxacin with no relapse after a follow up period of one year. To our knowledge this represents the first such reported case in South Africa. The role of ciprofloxacin in treating infections caused by multiantibiotic resistant S. typhi is also discussed.