Because of the central role of the sympathetic nervous system in mediating the stress response, plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured in 61 traumatically brain-injured patients to determine whether catecholamine (CA) levels obtained within 48 hours after injury provide reliable prognostic markers of outcome. Patient outcome was determined at 1 week using the Glasgow Coma Scale (GCS) and at the time of discharge using the Glasgow Outcome Scale (GOS). Levels of NE, E, and DA correlated highly with the admission GCS score (NE: r = 0.58, p less than 0.0001; E: r = 0.46, p less than 0.0025; DA: r = 0.27, p less than 0.04). Moreover, in the 21 patients with GCS scores of 3 or 4 on admission, NE levels predicted outcome at 1 week. All six patients with NE levels less than 900 pg/ml (normal level less than 447 pg/ml) improved to GCS scores of greater than 11, while 12 of 15 with NE values greater than 900 pg/ml remained with GCS scores of 3 to 6 or died. Levels of E and DA were not as useful. Catecholamine levels also increased significantly as the GOS score worsened. Levels of NE and E were significantly higher in patients who died or remained persistently vegetative than in those with better outcomes. In the 54 patients who survived beyond 1 week, significant correlations were present between the length of hospitalization and NE (r = 0.71, p less than 0.0001) and E (r = 0.61, p less than 0.0001) levels. Concentrations of NE (r = 0.61, p less than 0.0004) and E (r = 0.48, p less than 0.01) were also highly correlated with the duration of ventilatory assistance. Analysis of the interactions of CA levels and GCS scores, duration of ventilatory assistance, and length of hospitalization revealed that the CA's either enhanced the reliability of the GCS score or were independent predictors of outcome. Thus, these findings indicate that alterations in circulating CA levels reflect the severity of the neurological insult and provide support for the use of CA measurements as a physiological marker of patient outcome in both the acute and chronic phases of traumatic brain injury.