Histamine-containing neurons were visualized in Vibratome--sections of rat brain with the indirect peroxidase-antiperoxidase immunocytochemical method of Sternberger (Immunocytochemistry, 2nd edition, New York: John Wiley and Sons, pp. 1-354, '79) by utilizing a primary antibody directed against L-histidine decarboxylase (HDC). Cell bodies of HDC-immunoreactive neurons are located exclusively in the posterior hypothalamus: tuberal magnocellular nucleus (TM), caudal magnocellular nucleus (CM), and post-mammillary magnocellular nucleus (PCM). With the light microscope, all the HDC-immunoreactive neurons in CM and PCM and the majority of the HDC-immunoreactive neurons in TM appear to be large neurons, with a short, thick dendrite emerging from each pole of the long axis of the oval perikaryon and one or more, thinner, nonpolar primary dendrites. In the electron microscope, it can be seen that the immunoreaction product is diffusely dispersed in the cytoplasm. The ultrastructural features of all investigated (70) HDC-immunoreactive neurons in the three nuclei, independent of their light microscopic characteristics, are remarkably similar: large, unindented, pale nucleus; a high proportion of cytoplasm to nucleus (with the exception of the medium-sized HDC-immunoreactive neurons in TM); large, perinuclear array of Golgi apparatus; numerous mitochondria; endoplasmic reticulum fragmented into numerous small cisterns; thick initial portions of the primary dendritic trunks; few axosomatic synaptic contacts. Twenty-one Golgi-Kopsch-impregnated neurons taken from CM, PCM, and TM were embedded in epoxy resin, serially sectioned, and investigated in the electron microscope. The ultrastructural characteristics typical of HDC-immunoreactive neurons were observed in all three nuclei in neurons with large cell bodies tapering into two thick, sparsely spinous primary dendrites that subsequently dichotomize into very long (up to 100 microns), nontapering, aspinous secondary dendrites. In sections taken from the posterior hypothalamic area of rats prepared in a conventional way for electron microscopy, distinct populations of large cells can be observed in TM, CM, and PCM displaying the same set of ultrastructural characteristics as the HDC-immunoreactive neurons.