Noradrenaline innervation of the rat neocortex is studied by glyoxylic acid histochemistry and radioisotopic biochemical analysis. The data indicate that all neocortical areas receive a noradrenergic innervation which is identical in organization but varies in density from area to area. Radioisotopic analysis of catecholamines in the cortical areas studied reveals only the presence of significant levels of noradrenaline. Unilateral locus coerulus ablation greatly diminishes ipsilateral noradrenaline content and fiber innervation in all neocortical areas studied. Detailed histochemical analysis reveals a diffuse plexus-like arrangement of noradrenaline fibers, with each cortical layer having a distinctive pattern of innervation. Single noradrenergic fibers enter layer VI of cortex and branch at all levels to undergo extensive collateralization. Terminal horizontal branching in the molecular layer results in the most dense fiber plexus of all cortical layers. This pattern of noradrenaline innervation is similar to that of other non-specific afferent systems innervating neocortex.