The therapeutic effect of S-carboxymethylcysteine (S-CMC) on otitis media with effusion was investigated by use of immune-mediated otitis media with effusion (OME) induced in chinchillas. The S-CMC was administered daily to individuals in two different doses (100 mg/kg and 200 mg/kg) for 2 weeks after the induction of immune-mediated otitis media. The severity of OME was evaluated by observation of the tympanic membrane under a surgical microscope, by tympanogram, and by histologic findings of the middle ear mucosa. Results of the study showed that the oral administration of S-CMC at a dose of 200 mg/kg of body weight is more effective than at a dose of 100 mg/kg in the clearance of middle ear effusions in experimental OME. An autoradiographic study using 14C-S-CMC revealed that orally administered S-CMC is rapidly absorbed by the digestive tract and transported to the tubotympanum via the circulation. The uptake and excretion by secretory cells were apparently greater in activated secretory cells. However, S-CMC does not act on the infiltrating cells to prevent the release of chemical mediators such as histamine and prostaglandin E2. This finding suggests that prophylactic use of S-CMC may not be anticipated.