Pathophysiologic and clinicopathologic aspects of diabetic nerve disease are reviewed. Abnormal modes of impulse conduction in diseased nerves include decreased conduction velocity, temporal dispersion of impulses, frequency-related and total conduction block, abnormal cross-talk, and impulse reflection. Because structural and electrophysiologic variables (such as fiber geometry, ionic channel density, and properties of the extracellular milieu) vary with diameter, it is suggested that pathophysiologic mechanisms also should vary with diameter. Topographic patterns of clinical deficit, and their pathologic basis, are reviewed; it is suggested that lesions distributed at random along the length of the entire fiber may result in dysfunction that exhibits distinct proximal-distal gradients.