The effect of various doses of polyinosinic:polycytidilic acid (Poly I:C) in the range (0.25-250 micrograms/kg) administered i.v. on the body temperature of rabbits was investigated. The effect of ketoprofen on the febrile responses was also studied. The threshold dose of Poly I:C administered which produced a fever was between 0.25 and 0.5 micrograms/kg and a double-sigmoidal dose-response relationship was observed. A sigmoidal relationship was obtained with lower doses from 0.25 micrograms/kg to an apparent maximum with 2.5 micrograms/kg and another with higher doses from 5 micrograms/kg to another apparent maximum with 250 micrograms/kg. Ketoprofen (3 mg/kg) given s.c. 15 min prior to Poly I:C inhibited the production of fever. Ketoprofen administered after the onset of fever resulted in an immediate deffervescence. These results suggest that febrile responses to Poly I:C involve prostaglandin biosynthesis.