• The efficacy of sulfisoxazole prophylaxis was evaluated in 32 otitls-prone children in a double-blind cross-over clinical trial. During the sulfisoxazole therapy, seven patients (22%) had nine episodes of acute otitis media (AOM) while 20 patients (63%) receiving placebo had 36 episodes of AOM (P=.001). Although sulfisoxazole appeared to be beneficial in patients aged 2 to 5 years, statistically significant efficacy was noted only In children under 2 years of age. Otitis media with effusion persisting for more than five weeks was observed in ten children (31%) during sulfisoxazole therapy and in 14 children (44%) during the placebo period (P>.975). Sulfisoxazole therefore appears effective In preventing recurrent symptomatic AOM but not in reducing the frequency of persistent otitis media with effusion. The importance of careful follow-up of children receiving long-term sulfisoxazole therapy for prevention of recurrent AOM is stressed.