This report describes a case of ciprofloxacin treatment failure in a patient with enteric fever caused by Salmonella enterica serotype Paratyphi A. The organism was isolated from a blood culture from a patient who was treated with oral ciprofloxacin (500 mg every 12 h) for 13 days. The organism showed reduced susceptibility to ciprofloxacin (MIC 0.75 microg ml-1) and was resistant to nalidixic acid. The patient was then placed on intravenous ceftriaxone (1 g every 12 h) and responded within 3 days. The patient was discharged after 9 days on ceftriaxone with no relapse on follow-up. This case adds to the increasing incidence of treatment failures with ciprofloxacin in typhoid fever caused by typhoid salmonellae with reduced susceptibility to ciprofloxacin. It also highlights the inadequacy of current laboratory methods for fluoroquinolone susceptibility testing in adequately predicting in vivo activity of ciprofloxacin against typhoid salmonellae and supports calls for new guidelines for fluoroquinolone susceptibility testing of these organisms.