Substance P (SP) and the C-terminal sequences octa- and penta-SP produced dose-dependent vasopressor responses, and the action was associated with mild tachycardia. The vasopressor effect of SP was counteracted by the SP antagonist [D-Pro2,D-Phe7,D-Trp9]SP given intracisternally, suggesting that central SP receptors were involved. Experiments with different sodium contents in the vehicle and with naloxone pretreatment indicate that central naloxone-sensitive opiate receptors may exist, capable of modulating the effects of SP receptor activation.