The antipyretic response to arginine vasopressin (AVP) was investigated at 3 ambient temperatures using unanesthetized freely behaving male rats. Responses of non-febrile and febrile rats to intracerebroventricular (i.c.v.) injections of AVP and s.c. injection of indomethacin were observed at cold (4 degrees C), thermoneutral (25 degrees C) and warm (32 degrees C) ambient temperatures. In agreement with previous reports i.c.v. AVP at 25 degrees C decreased brain temperature of febrile but not non-febrile rats. This antipyretic effect was also observed at the warm ambient temperature and during cold exposure. Responses to s.c. indomethacin were qualitatively similar to i.c.v. AVP at neutral and warm temperatures. In the cold, however, indomethacin decreased the brain temperature of both non-febrile and febrile animals, although unlike AVP, brain temperature of non-febrile animals were decreased somewhat more than that of febrile animals. These data show that AVP decreases brain temperature of febrile more than non-febrile rats at all ambient temperatures and may therefore be acting partially on febrile set point. It is likewise clear that AVP affects specific effector mechanisms since antipyretic effects were of different magnitudes at different ambient temperatures. The observation that AVP and indomethacin have qualitatively similar effects on fever at the 3 ambient temperatures suggest that they may act via a common neural pathway.