The regional sympathetic responses during fevers induced by an exogenous pyrogen, lipopolysaccharide, and by two endogenous pyrogens, interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), were compared in urethane-anesthetized rabbits. Rectal temperature (Tre), ear skin temperature (Tear) as an index for cutaneous sympathetic activity, renal sympathetic nerve activity (RSNA) representing visceral efferents, arterial blood pressure, and heart rate were recorded during fever caused by intravenous injections of each of the three pyrogens. Lipopolysaccharide (1 micrograms/kg i.v.) caused prolonged fever of more than 3 h duration with a tendency towards a biphasic course of temperature, whereas fevers induced by IL-1 beta (1 microgram/kg i.v.) and TNF-alpha (10 micrograms/kg i.v.) were monophasic with a maximum between the 45th and 60th min. Each of the three pyrogens typically induced a decrease in Tear, indicative of cutaneous sympathetic activation, and simultaneous inhibition of RSNA during the first phase of rising Tre. RSNA tended to increase again approximately to its control level when the maximum Tre had been attained after the injection of each pyrogen. When the second rising phase of lipopolysaccharide fever started, Tear decreased once more, but RSNA remained at its control level. Taken together with the enhancement of IL-1 and TNF production during lipopolysaccharide-induced fever, the present results suggest the participation of these endogenous pyrogens in the responses of the sympathetic nervous system during the early phase of the lipopolysaccharide induced fever.