The most common complication of zoster in the elderly is postherpetic neuralgia, operationally defined as pain persisting longer than 1-2 months after rash. The cause of postherpetic neuralgia is unknown. Using polymerase chain reaction, we detected varicella zoster virus DNA in blood mononuclear cells from 11 of 51 postherpetic neuralgia patients, but not in any of 19 zoster patients without postherpetic neuralgia, or in any of 11 elderly individuals without a history of zoster. Blood mononuclear cells from nine of 27 serially-bled postherpetic neuralgia patients were positive for varicella zoster virus DNA; six were positive once, and three patients were positive more than once. Our results indicated that postherpetic neuralgia may be related to persistence of varicella zoster virus.