Injection (iv) of human urine into rabbits results in a fall in body temperature accompanied by peripheral vasodilation in a thermoneutral ambient temperature and suppression of shivering metabolism in the cold. There were no consistent changes in mean arterial pressure in response to the injection of urine. If the production of urine is prevented by occlusion of the ureters of rabbits, body temperature falls. Injection of endogenous pyrogen (iv) into rabbits, which have had their ureters occluded, results in a significant attenuation in the magnitude of the fever as compared to controls. These observations suggest that there is an endogenously produced cryogenic substance ("endogenous cryogen") normally excreted in an active form by the kidneys and which when either injected, or prevented from being excreted (by clamping the ureters), results in a regulated fall in body temperature. In addition, in human patients on regular dialysis treatment who still had residual renal function, the oral temperature was slightly below normal before hemodialysis and slightly above normal after hemodialysis, a difference averaging 0.39 degrees C (P less than 0.001). These data are in agreement with the hypothesis that endogenous cryogen is a dialyzable substance, and that its concentration is reduced (and therefore the patient's body temperature rises) during hemodialysis.