Influence of the duration of experimental fever on salicylate antipyresis in the rabbit.

1. Steady state fever has been produced in rabbits with a priming injection followed by a sustaining infusion of homologous plasma containing endogenous pyrogen (EP). This fever appears to last as long as the infusion continues.2. Intravenous salicylate given 1 h after the start of the EP infusion produced only a small antipyretic effect. The same dose of salicylate given 4 h after the start of an EP infusion resulted in rapid and progressive defervescence. Intermediate antipyretic responses were obtained when salicylate was administered intravenously 2 and 3 h after the start of an EP infusion.3. Less than 1% of the systemic dose, when injected into a lateral cerebral ventricle, produced a significantly smaller response at 1 h than at 4 h after the start of an EP infusion. At both these times the fall in temperature following the intraventricular salicylate injection was dose dependent, but the slope of the dose-response line was significantly steeper at 4 h than at 1 hour.4. It is suggested that salicylates produce their antipyretic effects by antagonizing the action of EP within the nervous system, and that the hypothalamic EP concentration falls during the course of an EP infusion.