High levels of neuropeptide Y (NPY) are found in the hypothalamus, median eminence, pituitary portal blood, and the pituitary in a number of species. Neuropeptide Y may influence the synthesis and secretion of a variety of hormones by interacting with specific receptors in the hypothalamus and/or the pituitary. To further define the function of NPY in the pituitary, we have examined the distribution of NPY immunoreactivity and NPY receptors in sections of human pituitary using immunohistochemical and autoradiographic techniques. Neuropeptide Y-immunoreactive varicose axons were seen throughout the neural lobe. A moderate number of NPY-immunoreactive cells were found in the anterior lobe. A very high level of [125I]PYY binding was seen in the neural lobe with low levels in the anterior lobe. The binding in the neural lobe was inhibited by NPY(13-36) at a Ki of 5.3 nM and [Leu31-Pro34]NPY at a Ki of 390 nM, indicating the receptor was the Y2 subtype. Therefore, neuronally released NPY may modulate human neural lobe function through a Y2 receptor.