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Patients with fever have a predisposition to experience dehydration, which may alter their thermoregulatory responses to elevated body temperature. In view of the recent discovery of the antipyretic activity of arginine vasopressin (AVP), it is possible that dehydration has a beneficial role during fever. Dehydration may enhance endogenous antipyresis by stimulating AVP release, making aggressive fluid replacement, which may inhibit AVP release, undesirable during fever. This study addressed the effects of manipulation of hydration status on temperature and cardiovascular responses in endotoxin-injected rabbits. Eight unanesthetized chronically instrumented rabbits were exposed to lipopolysaccharide (LPS) while in euhydrated state, after furosemide (5 mg/kg) and 24 hours of water deprivation (dehydrated), after infusion of saline (30 mL/kg) while in euhydrated state (hyperhydrated), and after saline (mL/per overnight body weight loss in grams) while in dehydrated state (rehydrated). Dehydrated rabbits display higher fevers that are biphasic in nature and are accompanied by increased vasoconstriction and duration of mean arterial pressure increases, indicating that activation of antipyretic mechanisms in dehydrated rabbits was not sufficient to reduce body core temperature. In addition, fluid supplementation in euhydrated rabbits did not alter the febrile response; however, a marked decrease in heart rate was noted. Furthermore, fluid supplementation in dehydrated rabbits significantly attenuates the rectal temperature and heart rate response to LPS injection, indicating the possibility that activation of antipyretic mechanisms of AVP in rehydrated rabbits was sufficient to reduce body core temperature. The results suggest that fluid supplementation has a beneficial role in keeping body temperature lower .