1. Micro-injections of prostaglandin E(1) (PGE(1)) into the anterior hypothalamus of the rabbit produced fever which was nearly immediate in onset. The prostaglandin sensitive region appears to be identical to that described as being fever sensitive to leucocytic pyrogen.2. Micro-injections of PGE(1) into the posterior hypothalamus and midbrain reticular formation of the rabbit did not produce fever.3. The febrile response to PGE(1) injected into the anterior hypothalamus was dose dependent over a range of 20-1000 ng.4. Ambient temperature influenced the thermoregulatory mechanism by which PGE(1) fever evolved. In the cold, PGE(1) fever was due to increased heat production while during heat exposure both evaporative and dry heat losses were reduced without significant changes in heat production. Vasoconstriction, confined mainly to the ears, was effective in producing fever in standard room environments (24-25 degrees C) along with a small increase in heat production.5. The preoptic anterior hypothalamic area retained its thermosensitivity during PGE(1) fever; heating this area attenuated, while cooling augmented the fever.6. The results support the view that PGE(1) is a mediator of pyrogen induced fever.