Crow-Fukase syndrome is a rare multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, skin changes and M-protein. We have examined levels of vascular endothelial growth factor/vascular permeability factor (VEGF) in serum with Crow-Fukase patients. Serum VEGF levels in Crow-Fukase syndrome were about 15 to 30 times higher than control and other neurological disorders. Most of the characteristic manifestations may be well explainable by the biological function of VEGF except polyneuropathy. We examined the direct effects of VEGF on blood nerve barrier function using blood brain barrier model of rat and intraneural injection of recombinant VEGF. As the result, VEGF affected blood nerve barrier and increased microvascular permeability, thereby inducing endoneurial edema. After increasing the permeability of the blood nerve barrier by VEGF, serum components toxic to nerves such as complements and thrombins may induce nerve damage. Our results suggest that overproduction of VEGF plays an important role in the pathogenesis of Crow-Fukase syndrome.