A porcine model was used to study the regional intracranial pressure (ICP) differences caused by a frontal mass lesion. Intraparenchymal ICP monitors were placed in the right and left frontal lobes, right and left temporal lobes, midbrain, and cerebellum. A frontal epidural mass lesion was created by placing a balloon catheter through a burr hole into the right frontal epidural space. A computer was used to acquire data from all monitors at 50-msec intervals. The balloon was expanded by 1 cc over a period of 1 second every 5 minutes and maximum pressure immediately before and during expansion was determined for each balloon volume at each site. Prior to expansion of the mass, the morphology of the cerebellum pressure tracing was different from that seen in all supratentorial regions. Also, pressures in the midbrain, at baseline, were slightly but significantly lower than pressures in the frontal and temporal regions. During expansion of the mass, a pressure differential that increased as the size of the mass increased developed between intracranial regions. Furthermore, the regional pressures were found to vary in a consistent fashion expressed by the formula RF=LF>RT=LT>MB>CB, in which RF and LF are the right and left frontal lobes, RT and LT are the right and left temporal lobes, MR in the midbrain, and CB is the cerebellum. The study shows that an expanding epidural mass reproducibly results in a gradient of brain parenchymal pressure. This gradient results in parenchymal pressures that are significantly different in each region of the brain depending on the proximity of that region to the epidural mass. The results of this study have implications for clinical ICP monitoring and therapy.