All patients admitted to a rehabilitation unit with closed-head injury over a 3-year period were reviewed for carbamazepine use exceeding 30 days in the hospital. Nine patients met the study inclusion criteria for age and duration of carbamazepine therapy. On review of the dose: serum concentration relationship, significant changes were noted in four patients. An initial increase in the dose: serum concentration ratio during the first few months of therapy was thought to reflect the well-known auto-induction of carbamazepine metabolism. However, unexplainable decreases in the dose: serum concentration occurred in the following months, and suggested alteration of carbamazepine pharmacokinetics in patients with traumatic brain injury. The finding may be important in determining the optimal approach to therapeutic drug monitoring of carbamazepine in brain-injured patients.