Secondary ischemic insults are common after severe head injury and contribute to poor neurological outcome. To study the increased vulnerability of the traumatized brain to secondary insults, bilateral carotid occlusion was produced after a controlled cortical impact injury in rats. The injury produced by either the impact injury or the bilateral carotid occlusion was mild to moderate when studied individually. The 1 and 3 m/sec impact injuries alone caused no detectable contusion at the impact side and minimal neuronal loss in the hippocampus. The 5 m/sec impact injury alone resulted in a small contusion with a median volume of 5.4 mm3. The 40-min period of bilateral carotid occlusion alone caused no cortical injury and no neuronal loss in the CA1 region of the hippocampus. When the 40 min of bilateral carotid occlusion was produced 1 h after the impact injury, there was an increase in the damage produced. The contusion volume was significantly larger after the 3 and 5 m/sec impact injuries and the hippocampal neuronal loss was significantly greater after the 1 and 3 m/sec impact injuries. When varying durations of bilateral carotid occlusion were produced 1 h after a 3 m/sec impact injury, contusion volume was significantly larger after bilateral carotid occlusion duration of 40 min, and CA1 neuronal loss was significantly greater after bilateral carotid occlusion durations of 30 and 40 min. When 40 min of bilateral carotid occlusion was produced at different time intervals after a 3 m/sec injury, the increased contusion volume was maximal when bilateral carotid occlusion occurred at 4 h after the impact injury, and the increased neuronal loss in the CA3 region of the hippocampus was maximal when bilateral carotid occlusion occurred at 1 h after the impact injury. By 24 h after the impact injury, 40 min of bilateral carotid occlusion had minimal consequences, similar to the effect in sham-injured animals. These results mimic the clinical situation where secondary insults of a severity that would not cause permanent neurological damage in a normal person are associated with a marked worsening of neurological outcome after head injury and where the injured brain is most susceptible to secondary insults in the first few hours after injury.