Injection of 0.03 micrograms capsaicin into one femoral artery elicited a fall in blood pressure in the rat. This effect was completely and reversibly abolished following intrathecal injection of 1 nmol of the specific substance P antagonist, [D-Pro2,D-Trp7,9] substance P. The capsaicin-evoked depressor reflex is therefore exclusively mediated by substance P-containing primary afferent fibres. Using spinal rats or decerebration experiments, the centre of the capsaicin-evoked reflex fall in blood pressure could be localized in the brain stem.