Clarithromycin is a new macrolide antibiotic that is activein vitroagainst a variety of organisms that are responsible for acute otitis media in children. The parent compound is metabolized to microbiologically active 14-hydroxy clarithromycin, which is especially active againstHaemophilus influenzae.The safety and efficacy of clarithromycin and amoxicillin suspensions were compared in the treatment of acute otitis media in children 1 to 12 years of age inclusive. This was a Phase III, single blind (investigator-blind), randomized, multicenter clinical trial. Clarithromycin oral suspension was given in a dose of 7.5 mg/kg (maximum, 500 mg) twice daily, and amoxicillin suspension in a dose of 20 mg/kg (maximum, 750 mg) was given twice daily for 7 to 10 days in a 1:1 ratio. Clinical evaluations were performed pretreatment, within 48 hours posttreatment and 10 to 14 days posttreatment. Myringotomy was performed in every child to obtain a microbiologic sample pretreatment and at subsequent visits as clinically indicated. A total of 79 children were enrolled, 39 in the clarithromycin and 40 in the amoxicillin treatment group. Thirty-two children were excluded from the efficacy analysis for various reasons. Clinical success (cure and improvement) rates at 0 to 4 days posttreatment were 93% for clarithromycin and 90% for amoxicillin (P> 0.999). Altogether 17 children (10 receiving clarithromycin, 7 receiving amoxicillin) experienced some adverse event, with gastrointestinal disorders being the most common complaint. No clinically significant differences in laboratory tests were found between the groups. This study showed that clarithromycin, 7.5 mg/kg/dose twice daily for 7 to 10 days, was as safe and effective as amoxicillin, 20 mg/kg/dose twice daily for 7 to 10 days, in the treatment of acute otitis media with effusion in children.