Investigations into the etiology of diabetic polyneuropathy have largely concentrated on the mixed peripheral nerve trunk. Although a number of workers have suggested that reductions in mixed nerve blood flow account for early diabetic polyneuropathy, experimental results remain controversial and are not fully sustained by human studies. Later disease is unquestionably associated with microangiopathy. Patients with diabetic neuropathy may have exclusive and severe sensory and autonomic involvement without obvious motor disease. The prominent sensory involvement in early diabetic polyneuropathy may suggest that the disease particularly targets dorsal root ganglia. Dorsal root ganglia (DRG) have features that might suggest they would be vulnerable to changes known to occur in diabetes, i.e. microangiopathy, excessive polyol flux and protein glycosylation. Autonomic ganglia may also be targeted early in the disease. The interest in using growth factors to treat diabetic neuropathy is at least partly based on the hypothesis that these agents might provide important trophic support for DRG neurons.