The existence of neocortical neurons displaying processes which penetrate the glia limitans (GL) and closely approach pial as well as intracerebral microvessels was determined in the dog from immunohistochemical localization of atrial natriuretic peptide (ANP). Scattered ANP-positive pyramidal somata located in cortical layers II and III displayed spinous dendritic arbors and delicate, beaded axon collaterals. Dendritic branches, as well as axon collaterals, traversed the GL near blood vessels entering the parenchyma, or encircled microvessels deep to the GL. These findings suggest that single ANP-like immunoreactive cortical neurons may monitor and control local cerebrovascular flow or permeability of the blood-brain barrier.