Continuing pain following herpes zoster is common in patients 60 years of age or older. Current treatments are generally unsatisfactory. The endogenous neuropeptide substance P is an important chemomediator of nociceptive impulses from the periphery to the central nervous system and has been demonstrated in high levels in sensory nerves supplying sites of chronic inflammation. In an attempt to alleviate the pain of 14 patients with postherpetic neuralgia, capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), known to deplete substance P, was applied topically to painful areas of skin for 4 weeks. Of the 12 patients completing this preliminary study, 9 (75%) experienced substantial relief of their pain. The only adverse reaction was an intermittent, localized burning sensation experienced by one patient with application of capsaicin. Although these results are preliminary, they suggest that topical application of capsaicin may provide a useful approach for alleviating postherpetic neuralgia and other syndromes characterized by severe localized pain.