Controversy exists over thermal versus nonthermal biological effects of microwave radiation. Rectal measurements of temperature, which are often used as indicators of thermal stress, may not be sufficiently reliable. In this investigation, the oxygen-consumption rate was used as a biological indicator of thermal stress from microwave radiation. Male CFI mice were irradiated with 2450-MHz CW microwave energy in a waveguide at forward power levels of 0 (sham), 0.09, 0.3, 0.6, 1.7, and 3.3 W, which resulted in corresponding averaged dose rates of 0, 1.6, 5.5, 10.4, 23.6, and 44.3 mW/g. The environmental conditions were: temperature 24 °C, relative humidity 55% and rate of air flow 78 ml/min. The rate of oxygen consumption of the mouse was determined for successive 5-minute periods by means of a paramagnetic oxygen analyzer, before, during, and after irradiation. Each of the stages lasted for 30 minutes. Across time, there was a reduction of oxygen consumption which correlated with a reduction in the averaged rate of energy absorption. The rate of oxygen consumption also decreased across time when the dose rate did not exceed 10.4 mW/g. The mouse apparently compensates homeostatically for large doses of microwave radiation by adjusting its metabolic rate downward to compensate for thermal loading from the radiation. Rebound of metabolic activity occurred after irradiation.