The efficacy of topical aspirin/diethyl ether (ADE) mixture in the treatment of acute herpetic neuralgia and postherpetic neuralgia, suggested in a previous open-label study (De Benedittis et al. 1992), has been evaluated in a double-blind crossover placebo-controlled study as compared with two other NSAID (indomethacin and diclofenac) drug/ether mixtures. The study included 37 patients (15 with acute herpetic neuralgia (AHN) and 22 with postherpetic neuralgia (PHN)). Comparative treatment results showed that only aspirin (but not indomethacin and diclofenac) was significantly superior to placebo, as compared with baseline and duration of pain relief (P < 0.05 and P < 0.01, respectively), in both AHN and PHN groups. Good-to-excellent results were achieved by 87% of AHN patients and by 82% of PHN patients treated with the ADE mixture, with no significant differences between the two groups. On the whole, patients with trigeminal involvement, less severe pain and with dysaesthetic quality of pain yielded best results.