A double-blind, randomized clinical trial comparing cefaclor with amoxycillin in the treatment of acute otitis media with effusion (OME) in infants and children is being conducted at Children's Hospital of Pittsburgh. Although the randomization code has not yet been broken, the results of treating the first 55 children are reported, since they appear to be of interest. Of the 62 ears with acute OME on which an initial tympanocentesis was performed, 41 positive cultures were isolated from the middle ear aspirates. Of the 10 ears from which Haemophilus influenzae was isolated, one had a type b strain, and of the remaining unencapsulated strains, one was resistant to both penicillin G and ampicillin. In the one ear from which Staphylococcus aureus was isolated, the organism was found to be resistant to ampicillin. However, all of the organisms were sensitive in vitro to cefaclor. In 88% of all subjects observed for the first 2 weeks, the initial symptomatic response was excellent. Six children had persistent signs and symptoms of acute OME and received a second tympanocentesis; however, none of the effusions from the repeat aspiration revealed an organism. An effusion was still present in 97% of the ears after 3 days, in 69% after 2 weeks, and in 48% 6 weeks after initiation of the study. Tympanocentesis did not appear to affect either the initial clinical response or the persistence of effusion. There were no adverse reactions to either drug in this study. Because an apparent increase in the incidence of ampicillin-resistant strains of H. influenzae is being reported, and because of the presence of ampicillin-resistant S. aureus in some ears with acute OME, a new antimicrobial effective against all the common pathogens causing acute middle ear disease would be desirable. In this respect, the preliminary findings of treatment with cefaclor from this study appear promising.