Oxidative stress is closely related to inflammation, a pathologic process characterized by activation of the transcriptional factor nuclear factor-kappa B (NF-kappaB). We have used transgenic NF-kappaB luciferase reporter mice to assess brain NF-kappaB activity noninvasively in living mice. We have studied NF-kappaB activation in hypoxic mice reoxygenated with either 21% O2 (room air) or 100% O2. Forty-one mice exposed for 2 h to 4% oxygen and then randomized to reoxygenation with pure oxygen or room air were investigated. A control mouse was dedicated to every mouse exposed to hypoxia. In vivo luminescence originated from brain was measured from mice 2 d before hypoxia, and 3 h after reoxygenation. A change in luminescence between the mouse exposed to hypoxia and its control demonstrates an alteration in NF-kappaB activity. Because of high mortality among males, only females were included. Six female mice died. Nineteen female mice were reoxygenated with room air, 16 with pure oxygen. We observed a significantly higher luminescence in the brain of the 100% O2 group versus the 21% O2 group. Our data indicate that brain NF-kappaB activity is increased in mice subjected to 4% oxygen followed by reoxygenation with 100% oxygen. However, when reoxygenation occurs with 21% O2 (room air), no elevation in NF-kappaB activity is observed. Thus, reoxygenation with room air may induce less brain inflammation than reoxygenation with pure oxygen.