HALOTHANE-anesthetized male rats were subjected to either moderately severe parasagittal fluid percussion- induced traumatic brain injury (TBI) or sham injury, and for 30 min immediately after injury hypoxia was induced in half the rats from each group by substituting a 13% O2source to deliver halothane for continued anesthesia. At 60 min post-TBI, Northern blot analysis showed a significant increase in c-fosmRNA levels, by 60–100% above sham control levels in the frontal cortex, cerebellum and hippocampus. Although hypoxia in sham-injured rats did not by itself alter c-fosmRNA levels, it did significantly potentiate the TBI-induced changes in c-fosmRNA in all three brain regions. These findings show that hypoxia is an important factor influencing genomic responses to TBI.