The subplate and marginal zone are prominent transient zones of the developing cerebral wall and contain a variety of neuropeptide Y-immunoreactive (NPY-ir) cells. This study investigates morphological maturation as well as regression and/or transformation of NPY-ir neurons in the transient compartments and the cortical plate of the human frontal cortex. The most prominent NPY-ir neuronal population is that of NPY-ir subplate neurons. They exhibited features of all subplate neuronal types reported in Golgi-impregnated sections, with the exception of the pyramidal type. The NPY-ir subplate neurons were the largest of all NPY-ir neurons, but their size regressed rather sharply between 1 month after birth and 2 years. In the NPY-ir subplate neurons and in the NPY-ir Cajal-Retzius cells of the marginal zone, signs of degeneration were observed between 36 postovulatory weeks and about 9 months after birth. Only a few subpial granular layer cells were NPY positive, and they exhibited degeneration-like features, such as cytoplasmic vacuolization, as early as 23 postovulatory weeks. However, NPY-ir neurons continued to be present in the adult counterparts of the subplate and marginal zone, i.e., gyral white matter and layer I, respectively. Across cortical layers II-VI, NPY-ir neurons had the hallmarks of all aspinous short-axon types, with the exception of the neurogliaform and the chandelier neuronal types. Some signs of degeneration were also observed among a few cortical NPY-ir neurons around birth. Unlike the NPY-ir subplate neurons, the general development of cortical NPY-ir neurons did not show an obvious decline in neuronal size and was similar to the pattern in Golgi-staining.