Epiglottitis in childhood is caused by Haemophilus influenzae type b. The usual antibiotic treatment at the Royal Children's Hospital, Parkville, Victoria is a five day course of chloramphenicol. Increasingly, third generation cephalosporins are being used to treat invasive H influenzae type b infections and preliminary data suggest that they can be used successfully for epiglottitis. In a prospective, randomised trial, the efficacy of a short course (two days) of ceftriaxone was compared with that of five days of chloramphenicol for the treatment of epiglottitis. The ability of these treatment regimens to eradicate H influenzae type b from the throat was also studied. Fifty five children were enrolled over an 18 month period. Epiglottitis was diagnosed clinically and confirmed on inspection of the epiglottis at direct laryngoscopy. Fifty three (96%) of 55 patients had H influenzae type b detected from at least one site: 44/52 (85%) from blood cultures, 41/47 (87%) from throat swab, and 6/8 (75%) as H influenzae type b urinary antigen. Children were randomised to receive either ceftriaxone 100 mg/kg intravenously followed by a single dose of 50 mg/kg 24 hours later (28 patients), or chloramphenicol 40 mg/kg intravenously, then 25 mg/kg eight hourly for five days, intravenously then by mouth (27 patients). All household contacts and patients receiving chloramphenicol received rifampicin 20 mg/kg daily for four days. Index patients randomised to ceftriaxone were not treated with rifampicin. There was no significant difference in outcome between the two groups with respect to the mean duration of fever, the duration of intubation, or the length of hospital admission. The proportion of patients colonised with H influenzae type b four weeks after discharge was not significantly different between the two groups: ceftriaxone 5/22 (23%) versus chloramphenicol and rifampicin 3/23 (13%). A short course of ceftriaxone was successful in treating all patients with no significant side effects and no relapses. A short course of ceftriaxone is a safe, efficacious, and economic alternative to the standard treatment in children with epiglottitis.