Cardiovascular and behavioral actions of substance P (SP) were examined after microinjection into the medial preoptic area (MPO), anterior hypothalamic area (AH), and ventral tegmental area (VTA) in conscious unrestrained rats. SP elicited marked increases in mean arterial pressure and heart rate as well as stereotyped behaviors of excessive grooming and exploring when injected into the MPO or AH. In the MPO, the latencies to the cardiovascular responses were observed after SP injection into the VTA. These results, together with our previous results, suggest that SP acts as transmitter or modulator in the rostral hypothalamic areas to elicit cardiovascular defense responses. In contrast, SP may not be involved in causing a defense reaction in the more caudal areas of the defense center.