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1. We have tested the hypothesis that a fever caused by pyrogen depends upon the synthesis of prostaglandin E in the brain and that the prostaglandin in turn acts on the hypothalamus to produce fever. 2. In rabbits, fever was produced by the injection of leucocyte pyrogen in a lateral cerebral ventricle. The latency, rate of rise and magnitude of the fever was unaffected by the simultaneous intraventricular injection of two prostaglandin antagonists, SC 19220 and HR 546. 3. Both antagonists effectively attenuated the fever caused by the intraventricular injection of prostaglandin E2. 4. This evidence is not consistent with the hypothesis that prostaglandin E is the principal mediator of fever.

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