Subdiaphragmatic vagotomy has been repeatedly shown to attenuate the febrile response to peripherally injected pyrogens. In the present study, we investigated whether vagotomy-induced attenuation of febrile responsiveness reflects a decreased sensitivity of the brain to central fever mediators, prostaglandin E2 (PGE2) and cholecystokinin octapeptide (CCK-8). Male rats were subjected to subdiaphragmatic vagotomy (or sham surgery) on day 0 and had a cannula implanted into the lateral cerebral ventricle on day 24. On day 30-36, the thermal responsiveness of the rats to PGE2 or CCK-8 was tested. Each animal was injected in the ventricle with either PGE2 (0, 10, 100, or 500 ng) in pyrogen-free saline with 0.5% ethanol (5 microl) or CCK-8 (0 or 1.6 microg) in artificial cerebro-spinal fluid (5 microl). While the 0-dose of either PGE2 or CCK-8 (vehicle alone) induced no thermal response, all the higher doses of either agent caused a body temperature rise preceded by tail skin vasoconstriction. The vagotomized rats did not respond differently than their sham-operated counterparts to any dose of either drug. It is concluded that subdiaphragmatic vagotomy does not change the rat's thermal responsiveness to intrabrain PGE(2) and CCK-8.