Capsaicin, the active ingredient in hot peppers, produces a long-lasting reduction of nociceptive reactions in rodents through a selective toxic action on afferent C-fibres. Immediate effects on C-fibre conduction are also found in other mammalian species and a reduction in nociceptive responses from human skin occurs following topical application. Direct application to nerve trunks may be expected to produce a useful degree of regional analgesia in man. Since this effect would occur without any anaesthesia or paralysis, it appears worth investigating as a treatment for pain of peripheral origin in man.