Neuropile glial (NPG) cells in the central nervous system of the medicinal leech, Hirudo medicinalis, were studied by histological, histochemical and immunocytochemical techniques. The NPG cells are often surrounded by electron-dense microglial cells. The central cytoplasm of NPG cells shows a significant zonation. The zone around the nucleus contains mitochondria, glycogen and vesicles. The cytoplasm also contains many ribosomes, a few dictyosomes and distinct inclusions up to 2 microns in diameter. A second zone around the perinuclear region is marked by the occurrence of bundles of intermediate filaments that correspond in thickness to glial filaments of vertebrates. We found a positive reaction with polyclonal antibodies against human glial fibrillary acidic protein (GFAP), and the areas of intense fluorescence correspond to the regions where intermediate filaments were found to be abundant. The peripheral zone contains numerous membrane stacks that could not be contrasted by lanthane nitrate or tannic acid. Therefore, the membrane stacks could be part of an extensive smooth endoplasmic reticulum, which is characteristic of cells with active lipid metabolism.