Generalized whole brain volume loss is well documented in moderate to severe traumatic brain injury. Whether this atrophy occurs in the thalamus and brainstem has not been systematically studied in children. Magnetic resonance imaging (MRI) quantitative analysis was used to investigate brain volume loss in the thalamus and brainstem in 16 traumatic brain injury subjects (age range 9-16 years) compared with 16 age and demo-graphically matched controls. Based on multiple analysis of covariance, controlling for age and head size, reduced volume in the thalamus and the midbrain region of the brainstem were found. General linear model analyses revealed a relation between processing speed on a working memory task and midbrain and brain stem volumes. Reduced volume in thalamic and brainstem structures were associated with traumatic brain injury. Reduction in midbrain and thalamic volume is probably a reflection of the secondary effects of diffuse axonal injury and reduction in cortical volume from brain injury.