Capsaicin has been used extensively as an experimental tool and in traditional and proprietary topical medications for acute soft tissue injuries. More recently it has been prescribed for several chronic pain conditions where it is usually administered topically for periods of several weeks. Here we have studied the consequences of this mode of application in the rat. Capsaicin cream (0.075% or 0.75%), or a vehicle cream, was applied twice daily to the hind paws of rats for a continuous period of 10 weeks. The hind paws treated with 0.75% capsaicin (but not 0.075%) because transiently hyperalgesic, but there were no signs of discomfort or distress associated with the treatment. After 10 weeks of capsaicin application, the ability of C fibres to produce neurogenic extravasation was markedly reduced. After 4 weeks of recovery this ability returned to normal in 0.075% capsaicin-treated animals, but remained impaired in the 0.75% group. This latter group showed a partial recovery 12 weeks after the end of treatment. The levels of substance P and CGRP in the sural nerve supplying the treated skin area were unchanged after both the 0.075% and 0.75% capsaicin treatments. The results suggest that the topical application of capsaicin at low concentration produces a reversible impairment of the terminals of C fibres in the skin without greatly exciting those fibres and without affecting the properties of cell soma. The number of afferent neurones in the L5 dorsal root ganglion projecting through the sural nerve was unchanged after 0.75% capsaicin treatment, suggesting that the topical capsaicin treatment does not produce any cell death in the adult animal.