Capsaicin selectively excites C-polymodal nociceptors in mammalian skin. In the rat, the only species so far studied in detail, a long-term desensitization of a subpopulation of C-polymodal nociceptors occurs after the initial excitation. After nerve treatment, permanent loss of some C-polymodal nociceptors is found in the rat. It is argued that capsaicin must act primarily on C fibres involved in signalling about pain and not itch, although there may be overlap between the C afferents involved in these two nociceptive sensations. The possibility is raised that C mechanoreceptors, with their good histamine sensitivity, are also involved in itch.