The forearm blood flow response to restoration of the circulation after arterial occlusion (reactive hyperemia blood flow (RHBF)) and to vigorous forearm exercise (exercise hyperemia blood flow (EXBF)) was measured with a strain gauge Plethysmograph in 9 patients with systemic amyloidosis and 20 normal subjects. The patients with systemic amyloidosis were clearly separated functionally into two groups. Four patients had striking reductions in RHBF as well as EXBF; all four had symptoms of peripheral vascular insufficiency, and the three of these patients who had a muscle biopsy showed severe infiltration of amyloid into the walls of arterioles. The remaining five patients without ischemic symptom had normal blood vessels on biopsy and did not differ significantly from the normal subjects. It is suggested that the exertional muscle discomfort experienced by some patients with systemic amyloidosis is at least in part the result of diseased arterioles, leading to a diminished arteriolar dilator capacity and compromised blood supply during exertion.