Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure on glucose metabolism in mice using [18F] 2-fluoro-2-deoxy-D-glucose (18FDG). Groups of male mice weighing approximately 30 g were studied. Group 1 was irradiated with a 137Cs source (9 Gy). Group 2 received full thickness burn injury on 25% TBSA followed by resuscitation with saline (2 ml, IP). Group 3 received radiation followed 10 minutes later by burn injury. Group 4 were sham-treated controls. After treatment, the mice were fasted for 23 hours and then injected (IV) with 50 µCi of 18FDG. One hour postinjection, the mice were sacrificed, and biodistribution was measured. Positive blood cultures were observed in all groups of animals compared to the shams. Increased mortality was observed after 6 days in the burn plus radiated group as compared to the other groups. Radiation and burn treatments separately or in combination produced major changes in 18FDG uptake by many tissues. In the heart, brown adipose tissue, and spleen, radiation plus burn produced a much greater increase (P < .0001) in 18FDG accumulation than either treatment separately. All three treatments produced moderate decreases in 18FDG accumulation (P < .01) in the brain and gonads. Burn injury, but not irradiation, increased 18FDG accumulation in skeletal muscle; however, the combination of burn plus radiation decreased 18FDG accumulation in skeletal muscle. This model may be useful for understanding the effects of burns plus irradiation injury on glucose metabolism and in developing treatments for victims of injuries produced by the combination of burn plus irradiation.