An antiserum directed against human dopamine-beta-hydroxylase purified from pheochromocytoma tissue was employed in an immunohistochemical study of the organization of the noradrenergic innervation of monkey neocortex. A detailed description is given of the laminar pattern of noradrenergic innervation in the dorsolateral prefrontal cortex (Brodmann areas 9 and 10) and the primary somatosensory cortex of the postcentral gyrus (Brodmann areas 3,1,2). The noradrenergic innervation of these two regions is similar in the following respects: (1) fibers are present in all six layers, (2) the innervation is dense and terminal-like in layers IV and V, and (3) layer VI is characterized by fibers oriented parallel to the pial surface which follow the contours of the subcortical white matter. However, these regions differ with respect to specific laminar patterns of fiber distribution and orientation and by virtue of the fact that the primary somatosensory cortex has a very dense noradrenergic innervation, while the density of innervation in dorsolateral prefrontal cortex is low relative to the postcentral gyrus and most other neocortical areas. The laminar pattern of noradrenergic innervation in primary visual cortex differs fundamentally from both prefrontal and primary somatosensory cortices. In a separate series of experiments, dorsolateral frontal cortex lesions were used to investigate the intracortical trajectory of noradrenergic fibers. A discrete aspiration lesion confined to the grey matter of the prefrontal cortex led to a substantial loss of noradrenergic fibers in cortical regions caudal to the lesion. The decrease in density of noradrenergic innervation was particularly pronounced in the pre- and postcentral gyri. These results demonstrate that while the noradrenergic innervation of primate cortex exhibits a far greater degree of regional variation than is present in the rat cortex, the tangential intracortical trajectory that is characteristic of the lissencephalic rat brain is also a dominant feature of the noradrenergic innervation of the gyrencephalic primate brain.