ACUTE otitis media is a common problem in infants and children. Although antibiotics seem to be effective in controlling suppurative complications, otitis is still a significant cause of morbidity and hearing loss. The etiology remains unsettled and treatment is largely empirical. Bacteriologic studies have repeatedly demonstrated that in only 60% to 70% of cases is it possible to isolate a pathogen from middle ear fluid.1-5 Unproved explanations for the sterility of the remaining 30% to 40% are diverse and include a possible viral etiology.5 There have been only sporadic accounts of virus isolation from middle ear fluid; few systematic attempts to isolate virus from middle ear fluid have been reported.5-8 The association of Mycoplasma with bullous myringitis has been observed in adult volunteers infected with artificially propagated M pneumoniae.9 In naturally acquired M pneumoniae infection the organism has been recovered on several occasions from the middle ear of older children 10,11 and consequently there has been renewed in¬ terest in investigating the role of this agent in otitis media, particularly in infants and young children.The present study was designed to in¬ vestigate the interrelationships among bacteria, viruses, mycoplasmas, and L forms in otitis media. A comparative evaluation of the effect of antibiotic ther¬ apy or placebo on the outcome was in¬ cluded. Some of the results of this portion will be presented in another publication.12Plan of Study One hundred and six patients aged two to 66 months were included. Although most of them had a bulging membrane with loss of normal light reflex and land¬ marks, in a few the eardrum was only diffusely red. In 65, the inflammation was bilateral. Sixty-one of the 106 patients had experienced previously one or more episodes of otitis media. Patients were excluded from the study for any of the following reasons: an associated bacterial infection requiring antibiotic therapy, antibiotic treatment during the previous ten days, a ruptured tympanic membrane, or an allergy to any drug used in the