Preschool-age patients (104) in a private pediatric practice were treated prospectively during colds with either decongestant-antihistamine or placebo to determine if the decongestant-antihistamine mixture was effective in the prevention of otitis media. Each child received a standard dosage of the study medicine according to a double-blind, crossover design. Otitis media was diagnosed on the basis of clinical criteria. Fifteen (6.4%) of 234 cold treated with placebo and 14 (5.8%) of 241 colds treated with the study drug were followed by otitis. The decongestant-antihistamine mixture was not useful in preventing development of otitis media in children with colds.