Prostaglandin E2 may not be solely responsible for hyperthermia produced by central administration of sodium arachidonate. To determine its effect, if any, on body temperature prostacyclin sodium salt, another product of prostaglandin endoperoxides, was injected into the third cerebral ventricle of unrestrained, unanesthetized cats while deep body temperature was recorded automatically. Doses of 2--25 microgram, in a volume of 0.05 ml saline solution, did not appreciably alter body temperature. A 100 microgram dose produced hyperthermia in five of six animals. Administration of 1 mg prostacyclin caused prolonged hyperthermic responses in four cats with a maximum increase in temperature of at least 2.1 degrees C. Prostaglandin E1 (1 microgram) produced hyperthermic responses which were intermediate between responses to 100 and 1000 microgram prostacyclin. Indomethacin (2 mg/kg), given IV to two cats during recovery from prostacyclin-induced hyperthermia, did not hasten the rate of recovery. These results indicate that, if a sufficient concentration of prostacyclin is achieved at a central site of action after injection of arachidonate or during pathologic processes which release arachidonic acid, prostacyclin could contribute to the development of hyperthermia.