BACKGROUND Chromophobe adenomas have been defined by the absence of secretory granules in them. But this definition has become doubtful since a granulation could be electron microscopically demonstrated. Hence we studied a collection of more than 100 surgically removed pituitary adenomas in order to find precise morphological criteria for the differential diagnosis of chromophobe adenomas, specially from the sparsely granulated chromophilic tumors. Furthermore we tried to find relations between the amount and type of granulation of the tumor cells and the clinical endocrine hyperfunction. METHODS 108 unselected pituitary tumors were studied by light and electron microscopic methods. For histology the tissue was fixed in Helly's fluid or in buffered formalin. The paraffin wax sections were stained with haematoxylin-eosin, PAS, gallocyanin-chrome alum, carmoisine L-orange G-wool green, Herlant's tetrachrome method, and performic acid-alcian blue-PAS-orange G. For electron microscopy small pieces of the tumor were fixed in buffered glutaraldehyde, postfixed in osmium tetroxide, and embedded in epon 812. Sections were stained with toluidine blue for light microscopy. Thin sections were stained with uranyl acetate and lead citrate. Electron microscopical pictures with a primary magnification of 4000 were semi-quantitatively judged for the content and the extent of rough endoplasmic reticulum, Golgi complexes, secretory granules, lysosomes, and mitochondria by a grading with 6 degrees. Results. With special stains and the electron microscope 46 adenomas could be identified which consisted only of slightly granulated or agranular cells but not of densely granulated cells. These were defined as chromophobe adenomas. Oncocytic adenomas were regarded as another tumor type and were not included. One half of the chromophobe adenomas showed ultrastructurally well developed protein-synthesizing organellas. The diameter of the secretory granules amounts up to 500 mum. One quarter had many autolysosomes or lipid droplets. On the other hand, 18 adenomas of our collection exhibited moderate acidophilic granulation with only a few denser or fully granulated cells. These were designated as sparsely granulated acidophilic adenomas. They were rich in organelles. 89% of them showed a well developed rough endoplasmic reticulum and large Golgi complexes as signs of high endocrine activity. The secretory granules had diameters between 200 and 600 upsilonm. The autolysosomes were for the most part small and rare. The 20 fully granulated acidophilic adenomas could be easily recognized and are not discussed in this paper. The sparsely granulated mucoid cell-adenomas were easily identified by a positive PAS-reaction. CONCLUSIONS From our studies we conclude that chromophobe adenomas exhibit only sparse granulation and no denser or fully granulated tumor cell...