Nerve impulses mediate every action, every sensation, and possibly every thought. Fifty years after Hodgkin Huxleyâ??s classic analysis of the nerve impulse in squid giant axons, it might be supposed that all that was worth knowing about nerve excitability was already known. Much, however, remains obscure about the normal function of the thinnest, unmyelinated (C) axons, and about the reasons that axons fail to conduct, or generate unwanted, ectopic impulses in disease. This laboratory has pioneered electrophysiological techniques for investigating human axons and their ion channels, ranging from direct patch-clamp recordings of single ion channel currents in biopsied nerve samples in vitro, to indirect, non-invasive measurements of nerve excitability properties in vivo, using threshold tracking. We have contributed evidence for the function of slow potassium currents, hyperpolarization-activated currents, and persistent sodium currents in human axons, and helped account for some types of ectopic nerve discharge. Current research is focussed in three main directions: the clinical application of nerve excitability testing, membrane properties of C fibres, and in vivo testing of muscle membrane properties.