The brain-specific S-100 protein was localized at the electron microscopic level in the anterior and posterior pituitary gland of adult rat by indirect immunoperoxidase histology. The protein was found in the stellate cells of the pars distalis and tuberalis, in the marginal cells that line the hypophyseal cleft and in the glia-like cells, the pituicytes, of the neural lobe. The pituicytes, the stellate cells and the marginal cells have in common at least two properties: they all express a brain-specific marker and they are satellite cells to the secretory axons in the neural lobe and of the secretory cells in the adenohypophysis. These properties suggest that the S-100 cells in the pituitary gland are neuroectodermal in origin, possibly glial in nature.