The parental administration of bacterial endotoxin to rats causes a hypothermia that is maximal after approximately 90 minutes. When endotoxin-injected rats were held in a controlled environment at 22C and 50% relative humidity and exposed for 90 minutes to microwaves (2450 MHz, CW) at 1 mW/cm, significant increases were observed in body temperature compared with endotoxin-treated, sham-irradiated rats. The magnitude of the response was related to power density (1 mW/sq. cm. > 5mW/sq. cm. > 1mW/sq. cm.). Saline-injected rats exposed for 90 minutes at 5 mW/sq. cm. (specific absorption rate approximately 1.0 mW/g) showed no significant increase in body temperature compared with saline-injected, sham-irradiated rats. The hypothermia induced by endotoxin in rats was also found to be affected by ambient temperature alone. Increases in ambient temperature above 22C in the absence of microwaves caused a concomitant increase in body temperature. This study reveals that subtle microwave heating is detectable in endotoxin-treated rats that have an impaired thermo-regulatory capability. These results indicate that the interpretation of microwave-induced biological effects observed in animals at comparable rates and levels of energy absorption should include a consideration of the thermogenic potential of microwaves.