Ofloxacin has been successfully used in the treatment of typhoid fever and Salmonella infectious of adults for many years. However, it has rarely been tried for the typhoid fever of children. In the present study, the therapeutic efficacy of ofloxacin in the treatment of typhoid fever in children was compared to that of co-trimoxazole. Out of 41 patients with bacteriologically documented typhoid fever, those with co-trimoxazole-resistant strains received 20 mg/kg ofloxacin twice daily for 10 days, and those with co-trimoxazole-susceptible bacteria were given 60 mg/kg co-trimoxazole twice daily for 10 days. Both groups were compared according to the clinical variables (apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms) and the time when cultures became negative. All patients in both groups were cured without relapse. Apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms were obtained in a significantly shorter time with ofloxacin than with co-trimoxazole (P < 0.05). The interval between onset of therapy and the time when cultures became negative was significantly shorter in the ofloxacin group than in the co-trimoxazole group (P = 0.005). Ofloxacin seems to be a good alternative in the treatment of typhoid fever caused by co-trimoxazole resistant salmonellae in children aged less than 16 years. It is well tolerated by the patients and it causes no side effects with short-term usage.