Abstract Thermoregulatory responses (rectal and ear skin temperatures, metabolic rate, respiratory rate), after treatment with N G-nitro- l-arginine methyl ester ( l-NAME), were investigated in normothermic and febrile rabbits at an ambient temperature of 20±1°C. In endotoxin challenged rabbits, l-NAME (25 mg/kg i.v.) given 30 min before LPS (1 μg/kg i.v.) significantly reduced fever response, while did not influence body temperature in saline treated animals. The antipyretic action of l-NAME was caused mainly due to inhibition of metabolic rate.