The levels of prostaglandin E2 (PGE2) were measured in aspirates of the effusion fluid from children suffering from secretory otitis media. The effects of naproxen 5 mg./kg. twice daily for eight weeks on the condition were studied in a placebo-controlled double-blind trial. Nineteen middle-ear aspirates from 13 children, six of whom had bilateral aspirations were examined. Detectable levels of PGE2 (greater than 1.0 ng. per ml.) were present in seven aspirates from seven children and ranged from PGE2 1.0 to 14.4 ng. per ml. In four of the six patients who had bilateral aspirations, PGE2 was detectable in the aspirate from one ear but not the other. However, the severity of otalgia and hearing loss was almost identical in the ears with detectable levels of PGE2 and those without. In a separate trial of naproxen, 11 patients received active drug and 13 received placebo. Naproxen had no significant effect on otalgia or hearing loss compared to placebo. These findings suggest that it is unlikely that non-steroidal anti-inflammatory drugs will be of therapeutic benefit in secretory otitis media.