Disturbed upper limb skin blood flow has been described in insulin-dependent (Type 1) diabetes mellitus, but the pathophysiological mechanism remains unclear. Hand skin blood flow was therefore measured at room temperature and following immersion of hands in cold and warm water in 13 healthy control subjects, in 10 patients with Type 1 diabetes mellitus and cardiovascular autonomic neuropathy, and a further 10 Type 1 diabetic patients with normal cardiovascular autonomic tone. Following cold challenge there was failure of digital artery clampdown in all diabetic patients in comparison with healthy control subjects (p less than 0.005), and the index finger temperature fell less (p less than 0.05). Laser Doppler flow was reduced at the palms at room temperature or following the warm challenge (p less than 0.008), as well as on the dorsum at room temperature (p less than 0.05), in all diabetic patients. In addition laser Doppler flow in the diabetic patients was reduced at the palms and dorsum immediately following cold water challenge (p less than 0.004) and this reduction persisted 15 min (p less than 0.05) and 30 min (p less than 0.01) into the recovery phase. In comparison to those diabetic patients with normal cardiovascular tone, those with cardiovascular autonomic neuropathy had reduced laser Doppler flow at the pulp 15 min after cold water immersion (p less than 0.05), at the nailbed immediately after cold water immersion (p less than 0.01), and at the palms immediately after warm water challenge (p less than 0.01).