• Thirty prepubertal boys with fragile X syndrome (fra[X]) were evaluated retrospectively to document the incidence of recurrent otitis media by physician records. The number of documented otitis media infections in the first five years of life was statistically more than those of the normal male siblings and of unrelated, cytogenetically normal controls. Nineteen (63%) of the 30 boys with fra(X) experienced six or more otitis infections. Of the 30 boys with fra(X), 13 (43%) were treated with polyethylene tubes or prophylactic antibiotics for persistent middle ear effusion. Males with fra(X) are at high risk for recurrent ear disease, which may exacerbate the cognitive, language, and behavior problems that exist in this syndrome.