Sixty-three patients with Salmonella typhi infections were randomly assigned to receive either ceftriaxone iv in single daily doses of 75 mg/kg for children and 3-4 g for adults for seven days or to receive 60 mg of chloramphenicol/kg a day orally or iv in four divided doses until defervescence and then 40 mg/kg a day to complete 14 d. In the ceftriaxone group, one death occurred, and two of seven patients still febrile 11 d after starting treatment were given chloramphenicol. In the chloramphenicol group, one death and one gastrointestinal perforation occurred. The probability of remaining febrile was similar for both groups during the first seven days but was significantly greater for patients receiving ceftriaxone during the 14-d period. Patients in the chloramphenicol group were more likely to be bacteremic on day 3. These results suggest that a seven-day course of once-daily ceftriaxone shows promise as an alternative to 14 d of chloramphenicol for treating typhoid fever.