The role of substance P (SP) in the regulation of sympathetic outflow to the cardiovascular system was assessed. Intrathecal injection(ith) of capsaicin caused a release of SP from the spinal cord and resulted in an increase in blood pressure and heart rate accompanied by an elevation of plasma adrenaline and noradrenaline. This pressor response was blocked by ith SP antagonist D-Pro2, D-Phe7, D-Trp9-SP or antiserum against SP. The immunohistochemical study showed that the SP-like immunoreactivity in T-8 of the spinal cord was decreased as the amount of capsaicin administrated was increased. Spinal cord transection had no effect on pressor responses caused by ith 10 micrograms capsaicin. These results suggest that SP transmits excitatory information to the cardiovascular system via spinal sympathetic pathway.