A histological, histochemical and ultrastructural study on muscle changes in chronic arterial insufficiency has been carried out in 40 patients. Muscle biopsy probes were taken in each patient either from the gastrocnemius or rectus femoris. In 7 patients submitted for amputation of a lower limb due to a more severe vascular disease, specimens were also obtained from both the sciatic and sural nerve for light and electron microscopic study. Our findings confirm the previous histological, histochemical and ultrastructural data on chronic ischemia of the skeletal muscle, suggesting that muscle damage is mainly based on a neurogenic noxa initiated by an ischemic peripheral neuropathy. In addition, many morphologic features also show the presence of a primary myopathic noxa, possibly depending on the direct damage of the mitochondrial respiratory chain by the deficit of the muscle blood supply.