When infused into the lateral cerebral ventricles of rabbits, human endogenous pyrogen (EP) preparations induced dose-dependent increases in slow-wave sleep concomitant with increasing body temperature. Heating EP to 70 degrees C destroyed its sleep-promoting and pyrogenic activity. Anisomycin (an antipyretic) prevented EP from increasing body temperature without affecting its sleep-promoting activity. Intravenous injection of EP induced fever and transient increases in slow-wave sleep but failed to induce prolonged increases in slow-wave sleep. We conclude that the somnogenic activity of EP is not secondary to its pyrogenic activity.