Substance P(SP)-immunoreactive cell bodies, axon terminals and SP receptors were widely scattered in most pressor areas. Lateral hypothalamus (LH) contains SPergic neurons; and SPergic fibers-SP receptors are present in LH projection areas; hence the role of SP in LH-pressor response was studied. The results showed that: (1) microinjection of glutamate into the lateral hypothalamus-perifornical region (LH/PF) or SP into LH projection areas: the locus coeruleus (LC), periaqueductal gray matter (PAG) or nucleus parabrachialis (NPB), respectively, all could induce pressor response; (2) preinjection of DPDPDT (a substance P antagonist) into the LC, PAG (but not NPB) reduced the LH/PF pressor response; (3) intra-RVL (rostral ventrolateral medulla) injection of phentolamine, propranolol or atropine also markedly attenuated the LH/PF pressor response. Taken together with our previous findings that alpha-, beta- and M-receptors in the RVL mediated the pressor response to excitation of LC, and alpha-, beta-receptors mediated the PAG-pressor response, it is suggested that the LH/PF pressor response may be brought about via the activation of LC- and PAG-RVL systems by SPergic fibers from the LH/PF.