Salmonella enterica serovar Typhi infection is widely prevalent in developing countries; its treatment has been complicated by the emergence of resistance to antimicrobial agents. Fluoroquinolones are orally administered antimicrobials effective against typhoid fever, including that caused by the multidrug-resistant S. Typhi. They are relatively inexpensive and more convenient to administer com pared to third-generation cephalosporins; hence, they constitute the drugs of choice for the treatment of typhoid fever in developing countries. In Asian countries, however, resistance to nalidixic acid-a prototype of quinolone antibiotics-diminishes the value of fluoroquinolones with regard to the treatment of typhoid fever. We experienced a case of nalidixic acid-resistant S. Typhi infection imported from Pakistan that was clinically refractory to ciprofloxacin treatment. A 31-year-old male presented with a fever of 14 days' duration after returning from his native Pakistan. Oral ciprofloxacin was empirically administered for three days without any beneficial effect. His illness, however, improved after the administration of ceftriaxone for three days. Blood culture revealed the presence of S. Typhi that was resistant to nalidixic acid (minimal inhibitory concentration > or =32 microgram/mL) but susceptible to ciprofloxacin (minimal inhibitory concentration=1.0 microgram/mL) in vitro.