This report describes the findings of a clinicopathologic correlative study of 18 cases of drusen of the optic nervehead and reports on the observations of the first ultrastructural study of this disease in the literature. From these observations, the processes of formation of drusen of the optic nervehead are proposed: abnormal axonal metabolism leads to intracellular mitochondrial calcification. Some axons rupture and mitochondria are extruded into the extracellular space. Calcium is heavily deposited in the extracellular mitochondria. Small calcified microbodies are produced and calcium continues to deposit on the surface of these nidi to form drusen. We conclude that drusen are definitely related to axonal degeneration of the optic nervehead.