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1. We have investigated the effects of endogenous monoamine depletion on the development of fever in rats. 2. Fever was produced in rats by a single intraperitoneal injection of Salmonella typhosa endotoxin or leucocyte pyrogen manufactured from ox blood. 3. Depletion of brain 5-hydroxytryptamine (5-HT) by pretreatment with p-chlorophenylalanine prevented the rise in rectal temperature produced both by bacterial endotoxin and by leucocyte pyrogen. 4. On the other hand depletion of noradrenaline (NA) by 6-hydroxydopamine pretreatment resulted in a potentiation of the fever produced by bacterial endotoxin. 5. These results suggest that 5-HT is involved in mechanisms responsible for the rise in temperature during fever and that NA is involved in mechanisms which serve to attenuate the rise.