Multidrug-resistant Salmonella typhi has spread to many parts of India, causing severe therapeutic problems. Of the 305 clinically suspected cases of enteric fever seen at Kasturba Hospital in Manipal, Karnataka between January 1990 and June 1991, Salmonella bacteremia was detected in 134 patients; 102 of these were caused by S. typhi. Eighty (78.4%) of the isolates from S. typhi-infected patients were resistant to conventional antibiotics used in the treatment of typhoid fever (i.e., ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole). No in vitro resistance was observed to ciprofloxacin, norfloxacin, and gentamicin. Major complications were seen in four patients infected by multiresistant S. typhi; three responded well to ciprofloxacin. The fourth patient died of hemorrhage and acute renal failure, even after receiving ciprofloxacin. In addition, less severe complications such as hepatitis and jaundice were observed in 12 other patients. Seventy-six of the multiresistant S. typhi belonged to phage type O biotype II and four were of untypeable Vi strains. The emergence of multidrug-resistant S. typhi has necessitated the use of fluoroquinolones in the therapy for enteric fever.