1Single applications of solutions of capsaicin were made to the intact skin of anaesthetized rats and the effects on cutaneous blood flow and the firing of C-nociceptor afferents determined. Blood flow was measured by laser-Doppler flowmetry. C-fibre activity was recorded from filaments dissected from the saphenous nerve. 2 Following the application of a capsaicin solution (concentration > 1 mM) to rat saphenous skin, low frequency firing occurred in C-polymodal nociceptors that sometimes continued for > 10 min. At the some time, large increases in skin blood flow occurred exceeding 300% in some instances. 3 After the initial excitation, some C-polymodal nociceptors lost their sensitivity to pressure whilst their sensitivity to heat was lost or enhanced depending on the vehicle used. 4 Sensitivity of C-polymodal nociceptors to heat recovered in <1 day following a single application of 33 mM capsaicin. Thresholds to mechanical pressure, however, were still significantly elevated by 123% on day 1, but had recovered on day 2. 5 Vasodilatation in response to saphenous nerve stimulation ('antidromic vasodilatation') was significantly reduced by 35%, 2 days after a single application of 33 mM capsaicin, but was normal at 4 days. 6 Following a single application of 33 mM capsaicin, skin substance P levels fell to only half the normal value at day I and remained at this level throughout the 4 day period examined. 7 It is suggested that the ability of relatively low concentrations of capsaicin to desensitize C-fibre nociceptors may underlie the analgesic action of topical capsaicin in man.