The pyrogenic response to supernatants from human blood monocytes stimulated with polyriboinosinic acid:polyribocytidylic acid (poly I:C) was characteristic of a response to endogenous pyrogen in that it was brief and monophasic, and was destroyed by heating the supernatants at 70 degrees C for 30 min. Pyrogen production was unimpaired when the incubations were carried out in the presence of cycloheximide (50 micrograms/ml; an inhibitor of protein synthesis) or indomethacin (50 micrograms/ml; an inhibitor of prostaglandin synthesis). Also, neither interferon, interleukins, tumor necrosis factor nor prostaglandin E2 were detectable in the supernatants from the poly I:C-stimulated human monocytes.