An attempt was made to evaluate the effectiveness of five antimicrobial agents in the management of 463 episodes of acute otitis media. Results were not discernibly different with tetracycline, erythromycin estolate, a "long-acting" mixture of penicillin G salts, and demethylchlortetracycline hydrochloride; not more than 6% to 15% of patients who received these agents required additional therapy. Administration of a triple sulfonamide preparation resulted in a failure rate of 22%, which was significantly higher than the failure rate in patients treated with tetracycline. No complications such as mastoiditis or meningitis were encountered, and myringotomy was performed in only four patients.