Hyperostosis cranii ex vacuo is diffuse thickening of the bones of the cranial vault that occurs in children following successful ventricular shunting for hydrocephalus. The bone changes are probably a physiologic response of the skull to a reduction in outward pressure exerted by the abnormally increased volume of cerebrospinal fluid. Based on the three examples portrayed, the authors suggest the mechanism of hyperostosis in these cases may be a physiologic response of the skull to diminution of the normal outward pressure, similar to the childhood cases of hyperostosis cranii ex vacuo. The underlying cause of brain atrophy in each of the cases was different, suggesting that thickening of the cranial bones is a consequence of brain atrophy, and is unrelated to the nature of the underlying initial insult. In case 1, brain atrophy followed a temporally discrete drug-related hypoxic-ischemic episode. Although skull thickness was not specifically assessed antemortem, a head CT scan report generated 10 years before death did not mention unusual cranial features. Brain atrophy in case 2 was a sequela of traumatic brain injury sustained in a motor vehicle accident. The remote cerebral changes in case 1 and case 2 had overlapping neuropathologic features, owing to the presence of superimposed ischemic damage in case 2. Brain atrophy in case 3 resulted from a primary neurodegenerative process unrelated to trauma or ischemia. Although the sample size was small, the authors' observations suggest that diffuse skull thickening in adult skeletonized remains may indicate that the individual had brain atrophy in life. This can aid in the identification of the decedent in human skeletal remains. 3 figures and 8 references