1. The antipyretic effect of arginine vasopressin (AVP) introduced into the brain by push-pull perfusion was investigated in the sheep. 2. Control perfusions with sucrose solutions had no effect on fevers induced by a bacterial endotoxin. Sucrose solutions containing AVP (4.0 microgram/ml.) perfused at 40 microliter./min had significant antipyretic activity, reducing the two peaks of the fever but had no effect on resting body temperature. 3. Loci in which AVP induced antipyresis were limited to the septal region about 2-3 mm anterior to the anterior commissure. 4. The amounts of AVP in perfusates from the septal region correlated negatively with changes in body temperature. 5. AVP administered I.V. did not lower fever. 6. AVP plasma levels correlated negatively with fever magnitude following premature birth induced by dexamethasone.