Volatile anesthetics increase the core temperature required to trigger sweating and decrease the core temperature required to trigger vasoconstriction. However, little is known about the effects of intravenous anesthetics on thermoregulation. We therefore tested the hypothesis that propofol increases the sweating threshold and decreases the vasoconstriction threshold, thereby increasing the inter-threshold range (core temperatures not triggering autonomic thermoregulatory responses). The study was conducted using a new model in which thermal manipulations were restricted to insensate skin, and sensate skin temperature was controlled. Six healthy, male volunteers were studied on 3 randomly ordered days: no propofol, target propofol blood concentration 2 micrograms/ml, and target blood propofol concentration 4 micrograms/ml. Each day, epidural anesthesia (approximately T11 level) was induced, using 2% 2-chloroprocaine (one volunteer received bupivacaine). Thermal manipulations were confined to the legs, and we attempted to maintain upper-body (sensate) skin temperature constant. Propofol was infused by a computer-controlled infusion pump. Volunteers were heated until sweating was observed, then cooled until fingertip vasoconstriction was observed. The sweating threshold was defined as the tympanic membrane temperature triggering sustained evaporative heat loss > 40 g.m-2.h-1. Similarly, the vasoconstriction threshold was defined as the tympanic membrane temperature triggering a sustained reduction in fingertip blood flow to < 0.25 ml/min. Central venous blood was assayed for propofol blood concentration. Increasing propofol concentration produced a linear decrease the vasoconstriction threshold (slope = -0.53 +/- 0.34 degrees C.microgram-1.ml-1; R2 = 0.98 +/- 0.04 [mean +/- SD]), but had little effect on the sweating threshold. The inter-threshold range was 0.51 +/- 0.46 degrees C during epidural anesthesia alone, and increased significantly, by 0.49 +/- 0.31 degrees C.microgram-1.ml-1 during propofol administration. Like volatile anesthetics, propofol reduces the vasoconstriction threshold and increases the inter-threshold range. However, propofol differs in leaving the sweating threshold unchanged.