This study evaluated the participation of µ-opioid receptor activation in body temperature (Tb) during normal and febrile conditions (including activation of heat conservation mechanisms) and in different pathways of lipopolysaccharide (LPS)-induced fever. The intracerebroventricular (i.c.v.) treatment of male Wistar rats with the selective opioid µreceptor antagonist D-Phe-Cys-Try-D-Trp-Arg-Thr-Pen-Thr-NH₂ CTAP (0.1-1.0 µg) reduced the fever induced by LPS (5.0 µg.kg^-1) but did not change Tb at ambient temperatures of either 20°C or 28°C. The subcutaneous (s.c.), i.c.v. and intra-hypothalamic (i.h.) injection of morphine (1.0-10.0 mg.kg^-1, 3.0-30.0 µg and 1-100 ng, respectively) produced a dose-dependent increase on Tb. I.c.v. morphine also produced a peripheral vasoconstriction. Both effects were abolished by CTAP. CTAP (1.0 µg, i.c.v.) reduced the fever induced by i.c.v. tumor necrosis factor- (TNF-, 250 ng), interleukin(IL)-6 (20.0 ng), corticotrophin-releasing factor (CRF, 2.5 µg), endothelin-1 (ET-1, 1.0 pmol), macrophage-inflammatory protein(MIP)-1 (500pg) and the first phase of the fever induced by prostaglandin(PG)F₂ (500.0 ng) but not the fever induced by IL-1(3.12 ng), PGE₂ (125.0 ng.) or the second phase of the fever induced by PGF₂. Morphine-induced fever was not modified by the cyclooxygenase (COX) inhibitor, indomethacin (2.0 mg.kg^-1). In addition, morphine injection did not induce the expression of COX-2 in the hypothalamus and CTAP did not modify PGE₂ levels in cerebrospinal fluid or COX-2 expression in the hypothalamus after LPS injection. In conclusion, our results suggest that LPS and endogenous pyrogens (except IL-1 and prostaglandins) recruit the opioid system to cause aµreceptor-mediated fever.