Sultamicillin, a dimer of ampicillin and a beta-lactamase-inhibiting agent, sulbactam, was given in oral form to 50 infants and children with acute otitis media. Tympanocentesis was performed on entry into the trial. Beta-lactamase-positive Haemophilus influenzae or Branhamella catarrhalis was isolated from 14 of 73 (19.2%) middle ear effusions in 9 children. Relief of symptoms (fever/otalgia) occurred in all children who completed therapy. However, in 8 children (16%), the antimicrobial agent was discontinued due to presumed adverse side effects (primarily gastrointestinal); vomiting which began prior to entry was noted in another subject who was withdrawn. An additional 14 children completed the course of treatment despite having diarrhea. Of the 41 children who completed drug therapy, 11 (26.8%) were effusion-free after 10 days, and 22 of 33 (66.7%) evaluable children were effusion-free after 6 weeks. Sultamicillin is a novel therapeutic approach to beta-lactamase-producing bacteria. In its oral form, however, diarrhea is a troublesome side effect.