Electrical stimulation within discrete sites of the spinal trigeminal complex in anesthetized or decerebrated rabbits results in arterial hypotension, often over 50 mm Hg, bradycardia of up to 60 beats/min, apnea, and gastric hypermotility, collectively termed the trigeminal depressor response (TDR). The threshold for the TDR is less than or equal to 10 muA and is graded up to 3-6 times threshold. It can only be elicited by trains of stimuli of low frequency (0.5-20 Hz); at 50 Hz the response disappears or becomes pressor. The bradycardia is only abolished by bilateral vagotomy combined with beta-adrenergic blockade, and thus results from combined excitation of cardio-vagal and inhibition of cardiac sympathetic nerves. The hypotension is unassociated with changes in cardiac output, does not change after blockade of the bradycardia, but disappears after alpha-adrenergic blockade and hence is entirely attributable to inhibition of ongoing sympathetic vasoconstrictor nerve activity. Below threshold stimulation the TDR can only be elicited from the root entry zone of the Vth nerve, from dorsal portions of the spinal tract of the Vth nerve, and to portions of the nucleus of the spinal tract, notably the nucleus caudalis. A TDR of reduced magnitude can also be elicited by low frequency stimulation of numerous branches of the Vth nerve arising from all three divisions and including the supra- and infra-orbital, the inferior alveolar, and lingual nerves. Bilateral electrolytic lesions of the nucleus tractus solitarii at the obex, with complete abolition of baroreceptor reflexes from carotid sinus and aortic depressor nerves, fail to alter the TDR elicited from the brain or from branches of the Vth nerve, or the vasodepressor responses elicited by electrical stimulation of the central ends of the IXth and Xth cranial nerves transescted distal to the branches of baro-receptor nerves. In contrast, caudal lesions of the trigeminal complex abolish the TDR elicited from brain and Vth nerve and substantially reduces the vasodepressor responses from the IXth and Xth nerves, without altering baroreceptor reflexes. We conclude that the TDR represents a heretofore recognized vasodepressor response dependent upon the spinal trigeminal complex which is at least in part anatomically distinct from pathways subserving arterial baroreceptor and somatic vasodepressor reflexes. The TDR can be reflexly elicited from widely distributed but yet unidentified receptors innervated by branches of the Vth and of the IXth and Xth cranial nerves other than those innervating arterial baroreceptors. It is of unknown function, but may be related to pain mechanisms.