There are marked regional variations in the laminar distribution and intensity of acetylcholinesterase containing fibers in cortex. These fibers were particularly prominent in the 5 major paralimbic (mesocortical) regions of the brain: the insula, the caudal orbito-frontal cortex, the temporal pole, the cingulate gyrus and the parahippocampal region. Within these 5 areas, the part of cortex which is adjacent to allocortex has the most acetylcholinesterase and there is a gradual decline towards granular isocortex. The primary sensory-motor areas have distinctive laminar patterns of enzyme distribution. For example, primary visual, auditory and somesthetic konio-cortices are characterized by a salient band in layer IV. On the other hand, motor and premotor areas are characterized by a concentration of radially arranged fibers within the deeper layers of cortex. High order sensory association areas throughout the cortical mantle consistently contain the least amount of acetylcholinesterase-positive fibers. It is conceivable that these patterns reflect regional variations in the distribution of cortical cholinergic innervation. The cortical topography of cholinergic markers may be relevant to the biological organization of mood and memory and also to the pathophysiology of Alzheimer's disease and of partial epilepsy.