Activation of the sympathetic nervous system attends traumatic brain injury, but the association of the severity of neurological impairment and recovery with the extent of sympathetic nervous system stimulation is poorly defined. In this study, plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured serially in 33 patients with traumatic brain injury and compared with the Glasgow Coma Score (GCS), which was obtained concurrently. A catecholamine gradient that reflected the extent of brain injury was demonstrated within 48 hours of the injury. In patients with a GCS of 3 to 4, NE and E levels increased four- to fivefold and the DA level increased threefold above normal (NE, 1686 +/- 416 pg/ml; E, 430 +/- 172 pg/ml; DA, 236 +/- 110 pg/ml), while patients with mild brain injury (GCS, greater than 11) had slightly elevated or normal levels. Patients with marked (GCS, 5 to 7) and moderate (GCS, 8 to 10) traumatic brain injuries had intermediate levels. The prognostic value of determining admission levels of NE was shown in patients with an admission GCS of 3 to 4 1 week after injury. Patients with severe and unchanging neurological impairment 1 week after injury had markedly elevated initial NE levels (2,176 +/- 531 pg/ml), whereas initial NE levels (544 +/- 89 pg/ml) were only mildly elevated in patients who improved to a GCS of greater than 11. These data indicate that markedly elevated NE levels predict outcome in patients with comparable neurological deficits. Thus levels of circulating catecholamines are excellent endogenous and readily quantifiable markers that appear to reflect the extent of brain injury and that may predict the likelihood of recovery.