A randomized clinical trial of chloramphenicol and ampicillin in the tretment of disease caused by chloramphenicol resistant S. typhi was performed. The chloramphenicol treated group did not respond as well as the ampicillin treated group in any characteristic examined: duration of fever, duration of positive blood and stool cultures, number of clinical failures and complication rate. Duration of bacteremia was a sensitive indicator of antibiotic efficacy. In regions where S. typhi resistant to chloramphenicol are common, patients suspected of having typhoid should be treated initially with either ampicillin or trimethoprim sulfamethoxazole until the results of antibiotic sensitivity testing are available.