Studies have shown that the dorsomedial hypothalamus (DMH) is a key region in the descending pathways mediating the cardiovascular response to emotional stress. We have recently demonstrated that the lateral/dorsolateral periaqueductal gray (l/dlPAG) is an important synaptic relay in mediating the tachycardic effect produced by activation of DMH neurons. This synaptic relay is mediated via NMDA excitatory amino acid receptors. In this study, our aim was to investigate, in conscious rats, whether activation of 5-Hydroxytriptamine 1A (5-HT(1A)) receptors in the l/dlPAG can attenuate the increases in heart rate and arterial pressure evoked by a) chemical activation of the DMH, b) air jet stress paradigm and c) chemical activation of l/dlPAG. Microinjections of the 5-HT(1A) receptor agonist, 8-OH-DPAT (1 nmol/100 nl), into the l/dlPAG reduced (by 62%) the increases in heart rate evoked by chemical activation of DMH neurons with the GABA(A) antagonist bicuculline methiodide (10 pmol/100 nl). The tachycardic and pressor responses evoked by air jet stress paradigm were also attenuated after treatment with 8-OH-DPAT in the l/dlPAG. The increases in heart rate and arterial pressure produced by microinjection of the excitatory amino acid receptor agonist, NMDA, into the l/dlPAG were largely reduced (by 94% and 73%, respectively) after treatment in the same region with 8-OH-DPAT. Taken together, our findings indicate that 5-HT(1A) receptors at the lateral dorsolateral PAG play a significant role in modulating the descending cardiovascular pathways from the dorsomedial hypothalamus and consequently the cardiovascular response to emotional stress.