Radiographs of the hands and feet of 19 diabetic patients with severe neuropathy were compared to those of 22 control patients without neuropathy. The two groups were matched for age, sex, and duration of diabetes. Cortical bone mass, measured by x-ray morphometry, was significantly lower in both the hands (p less than 0.002) and the feet (p less than 0.001) of those with neuropathy. The osteopenia was worse in the feet than the hands and also worse in women. Serum alkaline phosphatase levels were also significantly higher in the neuropathy group (p less than 0.005). Metatarsal fractures were a frequent finding in the neuropathic patients, but were not seen in controls. The presence of metatarsal fractures was strongly associated with the subsequent development of diabetic osteopathy (p less than 0.001). We conclude that cortical bone mass in the feet and hands is reduced in severe diabetic neuropathy. This may contribute to the predisposition to metatarsal fracture and diabetic osteopathy.