Dopamine (DA) and noradrenaline (NA) levels were estimated in the suprasylvian gyrus and the cerebellum of the cat and compared to those found in the cerebral and cerebellar cortex of the rat. As in the rat, DA was undetectable in the cerebellum and represented about 30% of the total catecholamine (CA) levels in the cerebral cortex of the cat. The uptake of [ 3H]DA was estimated in homogenates of the suprasylvian cortex, the caudate nucleus and the cerebellum of the cat. In the suprasylvian cortex the [ 3H]-amine uptake was partially reduced by desipramine alone or benztropine alone and more extensively inhibited in the presence of both inhibitors. In the cerebellum, the desipramine resistant [ 3H]DA uptake was insensitive to benztropine; conversely the benztropine resistant [ 3H]DA uptake was insensitive to desipramine in the caudate nucleus. The synthesis of [ 3H]CA from [ 3H]tyrosine was estimated in slices of the suprasylvian gyrus and of the cerebellar cortex of the cat and was compared to that obtained in cerebral and cerebellar slices of the rat. In both species, the [ 3H]DA/[ 3H]NA ratio was higher in the cerebral cortex than in the cerebellum. All these data suggest that catecholaminergic innervation in the cerebral cortex of the cat can be attributed, as in the rat, to dopaminergic as well as noradrenergic terminals. In further experiments, [ 3H]DA uptake was estimated in homogenates of the chronically isolated suprasylvian gyrus and compared to that of the contralateral side. [ 3H]DA uptake was markedly reduced 27 days after the operation and the residual [ 3H]amine uptake was not sensitive to benztropine or desipramine. Finally, [ 3H]CA synthesis from [ 3H]tyrosine was no more detectable in slices of the chronically isolated suprasylvian gyrus (27 days). These data reveal that both types of catecholaminergic terminals degenerate in the chronically isolated area and suggest the absence of dopaminergic interneurons in the cat neocortex. As a working hypothesis, it is suggested that the intermediary ascending catecholaminergic bundle is responsible for the dopaminergic innervation of the cerebral cortex. There is now little doubt that a dopaminergic system innervates the cerebral cortex of the rat. In this structure, after the selective degeneration of the ascending noradrenergic pathways induced by local 6-hydroxydopamine lesions, we have successively demonstrated: (1) the occurrence of an appreciable amount of dopamine (DA) 25; (2) a persistent [ 3H]DA synthesis from [ 3H]tyrosine, in vivo as well as in vitro in slices or purified synaptosomal preparations 24; (3) the existence of a specific DA uptake system sensitive to benztropine (a known inhibitor of DA transport in dopaminergic terminals) 23; (4) the histochemical visualization of a network of fine green fluorescent fibers (Berger et al., unpublished observations). Complementary results recently obtained by others support these findings. A DA sensitive adenyl cyclase has been demonstrated in cortical tissues of the rat 11. Dopaminergic terminals have also been identified in some areas of the cerebral cortex in unlesioned animals using combined histochemical and pharmacological methods 9,15. Catecholaminergic nerve terminals have also been observed in the cerebral cortex of the cat. It has generally been assumed that most of these terminals arise from noradrenergic neurons located in the locus coeruleus and in the subcoeruleus 1,17,20. However, even after severing all the ascending catecholaminergic bundles in the cat some catecholamine fluorescence still persisted in the neocortex 17. In this work we present biochemical evidence for the occurrence of both dopaminergic and noradrenergic terminals in the neocortex of the cat. Moreover, it is suggested that these terminals do not belong to cortical catecholaminergic interneurons, since both the synthesis of catecholamines (CA) and the specific uptake systems for DA and noradrenaline (NA) were no longer detectable in the chronically isolated cortical gyrus in which all afferent fibers have degenerated 6.