Intracerebroventricular injection of substance P (SP) has been reported to induce a typical cardiovascular defense response characterized by an increase in blood pressure, heart rate, sympathetic efferent activity, hindlimb vasodilatation and mesenteric vasoconstriction. In this study we employed microinjections of SP to localize the hypothalamic areas in which SP elicits the activation of the cardiovascular system. SP (550 pmol) injected into the anterior hypothalamus (AH) produced, after a short latency, a marked increase in mean arterial pressure and heart rate. In the ventromedial hypothalamus, the magnitude of the cardiovascular response to SP was identical to that in the AH, but the response was delayed. SP injected into the posterior hypothalamus failed to induce any cardiovascular response. These results suggest that the anterior and ventromedial parts of the hypothalamus are responsible for eliciting the central cardiovascular effects of SP in conscious rats.