Recent experimental data have shown that levels of matrix metalloproteinase-9 (MMP-9) increase after traumatic brain injury (TBI), degrading components of the basal lamina disrupting the blood-brain barrier. However, the post-traumatic secretion patterns of MMP-9 in humans are unknown. We measured the concentration of MMP-9 in plasma after TBI at the same time as the concentration of interleukin-6 (IL-6) in serum. Levels of MMP-9 and IL-6 in systemic arterial and jugular venous blood from seven patients with TBI were measured on days 0 and 1 post-injury. All patients underwent hypothermia at 32-35 degrees C as soon as possible after admission. Before induction of hypothermia, levels of MMP-9 in arterial and internal jugular venous blood exceeded the normal range. Higher MMP-9 levels were detected in internal jugular venous blood than in arterial blood. After hypothermia had been induced, MMP-9 levels in arterial blood and internal jugular venous blood decreased significantly, to within the normal range. In addition to these changes, a significant correlation was seen between levels of MMP-9 and IL-6 in internal jugular venous blood during the investigation period. These results indicate that MMP-9 is elevated in patients with acute TBI, and may play an important role in traumatic brain damage. The elevation of MMP-9 is associated with inflammatory events following TBI. Hypothermic intervention may suppress the elevation of MMP-9 with suppression of the inflammatory response, affording neuroprotection in TBI.