The effect of semipurified human leukocytic pyrogen isolated in vitro from neutrophilic leukocytes was studied in awake, chair-restrained rhesus monkeys. Intravenously administered leukocytic pyrogen elicited (1) a monophasic fever of short duration and latency to onset that varied from animal to animal and (2) a febrile response that was much greater at night, when the base-line temperature is low, than during the day, when the base-line temperature is high. Intravenous indomethacin, in contrast to large intravenous doses of sodium salicylate, reduced the febrile response to leukocytic pyrogen. Rapid, repeated injections of leukocytic pyrogen prolonged the febrile response from 1 1/2 to 5 1/2 hr, at which point there was a sudden 300%–400% increase in fever increment over a 30-min period. Since the rhesus monkey is as sensitive to human leukocytic pyrogen as the rabbit. it is proposed that this primate might serve as a useful model in investigations directed toward the understanding of the pathophysiology of fever in human beings.