Sulfisoxazole, 75 mg per kg per day, was administered for 13 weeks to all children with otitis media recurring at a rate of at least once every other month. The first 26 patients began prophylaxis during the months of January and February of 1979. To compare rates of otitis media with those in children not receiving concurrent prophylaxis during the same season, a matched control was randomly chosen as a child who began prophylaxis on the day nearest that when a study patient completed prophylaxis. The rates of otitis media during this same period were determined as the number of episodes per patient-month. Of the 26 treated patients, 11 had 16 episodes of otitis media in 72 patient-months (0.22 episodes per patient-month), in contrast to the 26 untreated patients who had 63 episodes in the same period (0.88 episodes per patient-month). This 75% reduction in incidence was statistically significant by X(2) analysis (P<.005). The two groups of children were comparable in age, sex, nursery school attendance, family history of allergy and number of episodes in the three months preceding chemoprophylaxis. These findings support the short-term chemoprophylactic use of sulfisoxazole for recurrent otitis media.