Thermoregulatory defenses are characterized by thresholds, the core temperatures triggering each response. Core body temperature is normally maintained within the interthreshold range, temperatures between the sweating and vasoconstriction thresholds that do not trigger autonomic defenses. This range usually spans only some 0.2 degrees C, but it remains unknown whether similar precision is maintained during the circadian core temperature cycle of about 0.8 degrees C. Accordingly, we evaluated the interthreshold range at four times of the day. We studied ten male volunteers, each at 3 a.m., 8 a.m., 3 p.m., and 8 p.m. At least 12 h elapsed between tests, and the order was randomly assigned. At each study time, volunteers were warmed peripherally until sweating was observed. Skin temperature was subsequently kept constant while core temperature was decreased by central-venous infusion of ice-cold fluid until peripheral vasoconstriction was detected. The volunteers were not permitted to sleep during threshold determinations, although sleep was not otherwise controlled. The core temperature triggering an evaporative water loss of 40 g.m-2.h-1 identified the sweating threshold. Similarly, the vasoconstriction threshold was defined by the core temperature triggering the initial decreases in plethysmographic finger tip blood flow. The interthreshold range at 3 a.m. was twice that observed at the other study times (P<0.05). Our data suggest that autonomic control of body temperature is reduced at 3 a.m., even when sleep is denied. This result contradicts the general perception that circadian variation alters the thermoregulatory target temperature, but not precision of body temperature control.