This study provides a semiquantitative description of the migration of the extracellular space marker, horseradish peroxidase (HRP), through the cerebral cortex. Following a continuous subarachnoid infusion of HRP, this marker was fixed rapidly within the cortical extracellular space (ECS) by intravascular aldehyde perfusion fixation. Microscopic measurements of the maximum depth of penetration of HRP into the cortex perpendicular to the pial surface were taken from coronal whole brain sections of rabbits that had been exposed to HRP for varying periods of time. The depth of penetration plotted as a function of time of exposure to HRP produced a 'diffusion profile'. The failure of experimental points to conform to an ideal diffusion curve indicates that simple diffusion alone is an inadequate explanation of the rate of movement of large molecular solutes from the subarachnoid space through the cerebral cortical ECS. The complex pattern of migration velocity of HRP through cortex may be due to alterations of flux of this solute which result from variations in the volume of ECS in different cortical laminae and to the presence of bulk flow of extracellular fluid in the deeper cortical regions.