d-Amphetamine has well-known behavioral and sympathomimetic effects in rodents, but its effects on thermoregulation are not well characterized. d-Amphetamine was administered i.p. to mice at doses of 0.1 to 10.0 mg/kg. Locomotor activity and preferred ambient temperature (Ta) were measured for 60 min after injection in a linear temperature gradient, and metabolic rate (MR) and evaporative water loss (EWL) were measured in a metabolic chamber at ambient temperatures of either 20 deg C or 30 deg C. Colonic temperatures (Tc) were obtained 60 min after injection in all cases. Doses of d-amphetamine at 0.3 mg/kg and above reduced preferred Ta from the control value of 30 deg C to about 25 deg C. The behavioral and autonomic heat loss responses induced in mice by d-amphetamine suggest that its thermogenic action is detected by the animal at doses below those producing measurable thermogenesis and that appropriate effectors, from selection of a cool Ta to increasing EWL, are engaged in an orderly progression to maintain normothermia under all but the most challenging conditions.