The induction of heme oxygenase-1 (HO-1), the 32 kDa heat shock protein, was examined in the traumatized rat brain. At 24 h after either mild of severe brain injury or sham surgery, HO-1 was immunolocalized in fixed sections on brain. After mild brain injury, hemorrhage was apparent in the subarachnoid space, external capsule and cerebellum. HO-1 was induced in similar areas in macrophages in the subrachnoid space and in glia in the cortex adjacent to the site of impact, the ipsilateral hippocampus, external capsule and cerebellum. After severe brain injury, extensive hemorrhage occurred in the external capsule, hippocampus and cerebellum. HO-1 was induced in glia in these areas of hemorrhage but was more extensive than that seen after mild injury and included the contralateral external capsule and hippocampus. These findings demonstrate remarkable induction of HO-1 in glia in the injured brain. Since heme is a potent inducer of HO-1, it is likely that the subrachnoid and/or intraparenchymal blood induced HO-1 in the glia where the heme was metabolized to biliverdin, iron, and carbon monoxide.