Abstract 1. 1. Rats pretreated with biogenic-amine depleting agents demonstrated significant alterations in rectal temperatures ( T re) in response to 1 hr of acute thermal stress. 2. 2. Depletion of norepinephrine (NE) caused a significant depression of equilibrium T re at 22°C and a greater depression of T re than controls in response to cold (6°C) stress. NE depletion also caused a significantly higher T re response to an acute heat (38°C) stress. 3. 3. Animals in which 5-hydroxytryptamine (5-HT) was depleted showed no significant difference in equilibrium T re at 22°C, and no significant difference in T re during cold stress, but a lesser rise in T re in the heat stress when compared to control animals. 4. 4. Simultaneous depletion of NE and 5-HT caused thermoregulatory responses et equilibrium and at 38°C similar to those produced by depletion of NE. 5. 5. It appears that normal thermoregulation during acute temperature stress may be disrupted by pharmacologic agents which deplete NE and 5-HT but it is still unclear whether the primary site of action of these agents is central or peripheral.