The authors studied 24 patients with a Glasgow Coma Scale score of 14 or 15 and normal computerized tomography scans after minor head injury. The study protocol included obtaining serial measurements of S-100 protein in serum during the first 12 hours after injury and early magnetic resonance (MR) imaging. Four patients (17%) had detectable levels of S-100 protein in serum. The S-100 protein levels were highest immediately after trauma, declining hour by hour. In two patients, MR imaging revealed intracranial contusion. Levels of S-100 protein were not detectable in serum in one patient with MR-verified cerebral contusion, but the first measurements were made late, 6 hours after trauma. The highest serum level of S-100 protein (0.9 microgram/L) was seen in a 73-year-old man 2 hours after injury. Magnetic resonance imaging revealed a contusion of the left cerebellar hemisphere, and the patient suffered permanent sequelae of impaired posture and dizziness.