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1. Sustained fever has been induced in conscious rabbits by I.V. injection and infusion of endogenous pyrogen. 2. Cerebrospinal fluid (e.s.f.) was sampled from the cisterna magna at hourly intervals. The concentration of prostaglandin increased in parallel with rectal temperature. The prostaglandin was identified as one of the E series. 3. When sodium salicylate (1-5 m-mole followed by a continuous infusion of 9 mumole/min) was started 1 hr before endogenous pyrogen, the febrile response to the pyrogen was not significantly diminished but no rise of prostaglandin concentration was detected in c.s.f. 4. This dissociation between fever and prostaglandin concentration means that changes in cisternal prostaglandin concentration cannot be accepted as evidence that prostaglandin mediates the febrile response.