Peripheral neuropathy plays an important part in the development of foot complications in patients with diabetes. We studied the contribution of impairment of the dual sensory and inflammatory function of unmyelinated nociceptive C fibers in the foot complications of diabetes. The integrity of these fibers was assessed objectively by measuring axon reflex vasodilation in response to stimulation with 10 percent acetylcholine introduced by electrophoresis. This was related to the non-neurogenic capacity of the vessels to dilate in response to a mechanical stroke. These measurements were made on the soles of the subjects' feet. The function of the nociceptive C fibers was abnormal in 1 of 14 patients with longstanding diabetes who had no foot complications, 3 of 9 patients with diabetes and skin sepsis, 8 of 11 patients with typical neuropathic plantar ulcers, and all of 8 patients with neuroarthropathy. In patients with longstanding diabetes but no foot complications, the mean ratio of neurogenic to non-neurogenic vasodilation was not significantly different from that in controls; however, it was significantly lower in the other three groups (P less than 0.01 for those with sepsis; P less than 0.001 for those with ulcer or arthropathy). Impairment of the neurogenic vasodilator response, or flare, correlated with the clinical diminution of pain sensation. This study suggests that the loss of both components of nociceptive C-fiber function--neurogenic inflammation and pain sensation--is an important factor in the development of foot complications in diabetes.