The status of 12 patients after severe traumatic brain injury was investigated to determine the clinical significance of serum osteocalcin levels during the active phase of neurogenic heterotopic ossification. The diagnosis of heterotopic ossification was confirmed on the basis of radiologic findings. The mean interval between the initial injury and diagnosis of heterotopic ossification was 29 weeks. At the time of diagnosis, serum osteocalcin and total alkaline phosphatase levels were determined along with 24-hour urinary calcium and hydroxyproline excretion. The mean serum osteocalcin level was normal at 4.3 ng/ml (normal range 1.6-6.6 ng/ml) in contrast to the elevated mean values for serum alkaline phosphatase (mean = 173 units/liter; normal range 0-105 units/liter) and urinary hydroxyproline concentration (mean = 39.6 mg/24 h; normal range 7-25 mg/24 hr). Only 17% of the subjects demonstrated an elevated serum osteocalcin level, whereas 58% of the patients had an elevated serum alkaline phosphatase level. Urinary calcium excretion and hydroxyproline excretion were elevated in 33% and 70% of subjects, respectively. These data did not reveal a significant correlation between serum osteocalcin and serum alkaline phosphatase, urinary calcium excretion or urinary hydroxyproline at the time of diagnosis or in serial measurements. Therefore, serum osteocalcin is not a valuable adjunct in confirming the diagnosis of neurogenic heterotopic ossification once the diagnosis has been suggested on the basis of clinical findings and it does not appear to play a role in assessing the maturation of heterotopic ossification.