To explore the possibility that salicylates can stimulate VE via an extracranial mechanism, heads of dogs were perfused entirely by a support dog with blood of unchanging gas composition; spinal cord remained intact. The carotid bodies lay within the region of the perfused head; the aortic bodies were denervated. Intra-arterial infusion of sodium salicylate (150-225 mg/kg) into the body of these head-perfused animals elicited large increases in VE (188+/-11%), although significant amounts of salicylate did not reach the head or carotid body. In any case, when the same dose of salicylate was selectively administered to the head, increases in VE were limited to 23+-8%. To determine the contribution of thoracic receptors to the increase in VE elicited by salicylates, a subsequent group of head-perfused animals underwent complete spinal transection at the first lumbar level. Nnetheless, intra-arterial infusion of sodium salicylate (150-225 mg/kg) into the body of these head-perfused animals still elicited large increases in VE (111+/-13%). It is concluded that thoracic receptors (other than the aortic bodies) mediate a significant portion of the increase in VE elicited by intra-arterial infusion of sodium salicylate.