It has been suggested that Ménière's disease is part of a polyganglionitis in which symptoms result from the reactivation of neurotropic virus within the internal auditory canal, and that intratympanic applications of an antiviral agent might be an efficient therapy. In 2002, we performed a pilot study ending with encouraging results. Control of vertigo was achieved in 80% of the 17 patients included. We present here a prospective, double-blind study, with a 2-year follow-up, in 29 patients referred by ENT practitioners for a surgical treatment after failure of a medical therapy. The participation in the study was offered to patients prior to surgery. A solution of ganciclovir 50 mg/ml or of NaCl 9% was delivered for 10 consecutive days via a microwick inserted into the tympanic membrane in the direction of the round window or through a ventilation tube. One patient was withdrawn from the study immediately after the end of the injections. He could not complete the follow-up period, because of persisting vertigo. As he had received the placebo, he was then treated with the solution of ganciclovir. Symptoms persisted and he underwent a vestibular neurectomy. Among the remaining 28 patients, surgery could be postponed in 22 (81%). Surgery remained necessary to control vertigo in 3 patients from the group that received the antiviral agent, and in 3 from the control group. Using an analogical scale, patients of both groups indicated a similar improvement of their health immediately after the intratympanic injections. The scores obtained with a 36-item short-form health survey quality of life questionnaire and the Dizziness Handicap Inventory were also similar for both groups. In conclusion, most patients were improved after the intratympanic injections, but there was no obvious difference between the treated and control groups. The benefit might be due to the middle ear ventilation or reflect an improvement in the patients' emotional state.