Intracerebroventricular (i.c.v.) injection of human recombinant interleukin-6 (IL-6; 20–100 ng) caused significant increases in colonic temperature and resting oxygen consumption [Formula: see text] in conscious rats. These effects were prevented by pretreatment with a cyclooxygenase inhibitor (flurbiprofen, 1 mg/kg, i.p.) or a corticotrophin-releasing factor antagonist (α-helical CRF 9–41, 25 μg, i.c.v.). Higher doses of IL-6 (i.c.v.) caused only small changes in [Formula: see text] and temperature, and very high doses given intravenously (i.v.) (4 μg/kg) were required to stimulate these parameters. Central injection of anti-rat IL-6 antibody inhibited the effects of interleukin-1β (i.c.v.) or endotoxin injection (i.p.) on colonic temperature and [Formula: see text] in conscious rats. These data indicate that IL-6 is an important endogenous pyrogen that acts within the central nervous system.Key words: interleukin 6, fever, thermogenesis, brain, pyrogen.