Neurotropic viruses have been postulated to play a role in the development of Meniere's disease (MD). The purpose of this study was to evaluate the endolymphatic sacs of patients undergoing surgery for MD in a single-blind study for evidence of herpes simplex virus (HSV), varicella zoster (VZ), or cytomegalovirus (CMV) DNA. Polymerase chain reaction (PCR) was used as the method of detection because of its sensitivity, specificity, and applicability to fresh, as well as fixed tissues. Twenty-two patients with MD and 11 control patients with vestibular schwannomas had a portion of the endolymphatic sac removed at the time of surgery. The specimens were then evaluated for herpes simplex type 1 and 2, varicella zoster, and cytomegalovirus DNA. Herpes simplex virus DNA was detected in 2 of the 22 extracts from the endolymphatic sacs obtained from patients with MD. There was no evidence of a positive signal obtained with any of the other viral DNA probes when PCR was performed on the control tissue extracts or the other MD tissue extracts. These results do not demonstrate a significant difference and do not statistically support the postulate that ongoing viral infection in the endolymphatic sac is a frequent factor in the development of Meniere's disease.