Antigens of respiratory viruses were tested by immunoassay of the middle ear fluids and nasopharyngeal secretions of 137 children with acute otitis media. The following were found: (1) an epidemic of infection with respiratory syncytial virus (RSV) caused a significant increase in the occurrence of acute otitis media. (2) Fifteen percent of the children had RSV antigens in middle ear fluid, and in 7% RSV was the sole pathogen found. Adenovirus antigens were found in the middle ear fluid of 3% of the children. (3) Bacteriologic findings in otitis media related and unrelated to viral (RSV) infection were similar. These findings indicate that some episodes of otitis media are associated with viral infection and that the disease may be solely due to viral infection. Thus, at least during an epidemic of respiratory virus infections, treatment failures--e.g., fever and earache unresponsive to antimicrobial therapy--may be due to a viral etiology of acute otitis media.