A description is given of the electron microscopic-morphometric findings obtained for the islets of Langerhans of the pancreas and for the glucagon-producing A cells of one patient suffering from longstanding insulin-dependent diabetes mellitus (IDDM, type I diabetes), two patients with longstanding insulin-independent diabetes mellitus (NIDDM, type II diabetes), and one non-diabetic. A morphometric determination of the volume densities of the vascular connective tissue and the various endocrine cells per islet tissue and organelles/ultrastructures per A cell was made, and the diameters of the A-granules were measured. So far, no such studies have been made for human diabetes mellitus, and only a few are available for humans with sound metabolism. In general, the qualitative and, particularly, the quantitative electron microscopic results found for the IDDM patient show greater and clearer deviation from the control with normal metabolism than the findings obtained for the NIDDM patients. As regards the cellular composition of the pancreatic islets and changes caused by diabetes mellitus, the morphometric values obtained from electron micrographs are in essential agreement with comparable findings reported in the literature for light microscopic-histochemical and -immunohistochemical morphometry. The patient with insulin-dependent diabetes has a higher proportion of vascular connective tissue in the pancreatic islets than the non-diabetic. This increase is both relative and absolute and is primarily connected with the loss of B cells in this type of diabetes. In the IDDM patient, A cells were found in the islets but also scattered as single cells in the exocrine tissue and in the walls of pancreatic ductules. The ultrastructural composition of the A cells varies within wide limits even in persons with sound metabolism. Diabetes mellitus does not cause major qualitative alterations in the A cells. The A cells of the IDDM patient contained a remarkable number of nuclei and rarely showed A-granule crinophagia. The casuistic electron microscopic findings, most of which have been obtained for the first time, are discussed. Nothing can be said at this stage about the general applicability of the findings. The morphometric results obtained for the A cells can be interpreted as indicating increased metabolism with heightened glucagon synthesis and secretion in the case of the insulin-dependent diabetic and, to a lesser extent, in the NIDDM patients. This interpretation would support the assumption of a normally existing mutual local paracrine regulation of the A and B cells which stems from close topographical relations (contact, gap junctions).