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Otitis media (OM) develops in the first months of life and persists throughout childhood in many rural Aboriginal children. We have followed Aboriginal and non-Aboriginal infants from birth to determine the relationship of the early onset of OM to nasopharyngeal colonization with respiratory pathogens. Aboriginal infants were colonized with multiple species of respiratory bacteria (Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae) at a rate of 5% per day and the timing of colonization predicted the onset of persistent OM in individual Aboriginal infants. Non-Aboriginal infants became colonized by M. catarrhalis alone at the slower rate of 1% per day and experienced transient episodes of OM in the absence of colonization. We attribute early bacterial colonization in most Aboriginal infants to high rates of cross-infection due to overcrowding, poor hygiene and high rates of bacterial carriage. Early age of infection and the multiplicity of bacterial types may contribute to prolonged carriage and to eustachian tube damage leading to persistent OM. Thus Aboriginal infants are “otitis-prone” and might qualify for prophylactic antibiotics.