The effect of orthostatic changes in vascular transmural pressure on blood flow in subcutaneous tissue was studied in 10 patients with the acrosclerotic type of generalized scleroderma. Blood flow was measured on the back of the hand by the local 133xenon washout technique. The blood flow remained constant when the hand was elevated 20 cm above the jugular notch, indicating that there is autoregulation of blood flow, When the hand was lowered 40 cm below by 50% observed in normals. Thus, intrinsic vascular reactions responsible for the autoregulator response are present, whereas the normal "vasoconstrictor response" to an increase in venous transmural pressure is almost abolished in tissues with sclerodermic changes. The abolition of the vasoconstrictor response is probably due to sympathetic neuropathy associated with the sclerodermic changes.