We determined the course of otitis media in a prospective, longitudinal study of infants who were enrolled at birth and followed to age 1 year. Bilateral chronic otitis media with effusion developed in eight of 24 (33%) with onset of otitis media before age 2 months, compared to two of 30 (7%) with later onset (P = 0.012). Infants with bilateral chronic otitis media with effusion could be identified early: eight of 15 (53%) infants with bilateral middle ear effusion at age 2 months subsequently had bilateral chronic otitis media with effusion, compared to two of 55 (4%) infants without bilateral effusions at age 2 months (P = 0.000007). The onset of otitis media was symptomatic in 29 of 54 (54%), and asymptomatic in 25 of 54 (46%). If regular well-child examinations with otoscopy had not been performed in asymptomatic infants, bilateral chronic otitis media with effusion would not have been detected in six of 10 infants. Infants with otitis media in early infancy may be asymptomatic and are at high risk for chronic otitis media with effusion.