The morphology, laminar distribution, and distribution relative to cytochrome oxidase patches of neuropeptide-Y immunoreactive (NPY-ir) neurons were studied in the human striate cortex. The density of NPY-ir cells was highest in the white matter. NPY-ir neurons were sparsely distributed within the cortical layers. NPY-ir neurons were located in both cytochrome oxidase dense patch and interpatch regions. However, the paucity of NPY-ir neurons in layer III, where cytochrome oxidase patches are most clearly demonstrated, precluded establishing a clear relationship of NPY-ir neurons to cytochrome oxidase patches. NPY-ir neurons exhibited a variety of nonpyramidal morphologies, and many of them had axons with recurrent or looped trajectories. A dense plexus of NPY-ir axons was located just beneath the pia, and these axons were concentrated at the entry points of pial blood vessels. Other NPY-ir neurons had cell bodies or processes in close proximity to cerebral capillaries. These results suggest a role of NPY in cortical metabolism, control of cerebral circulation, or activity-related changes in local blood flow.