Primary amyloidosis and myeloma associated amyloidosis causes neuropathy in 10% of the cases, and hemodialysis associated amyloidosis causes carpal tunnel syndrome. However, most severe amyloid neuropathy is observed in familial amyloidotic polyneuropathy (FAP). FAP type I is an autosomal dominant systemic amyloidosis characterized by sensory dominant systemic amyloidosis characterized by dissociated sensory disturbance and autonomic dysfunction. Amyloid deposition is noted universally in endoneurium of peripheral nerve, especially prominent in sural, sciatic nerve, dorsal root ganglia and sympathetic ganglia. Moderate deposition was also noted in dorsal spinal root. Amyloid was absent in CNS. The number of small myelinated fibers is decreased. Unmyelinated axons are severely depleted and amyloid fibrils are observed around the wall of small vessels. Amyloid fibril protein consists of variant transthyretin (TTR:prealbumin) with one amino acid substitution of methionine-for-valine at position 30. Other types of FAP show another one point mutation in TTR molecule. Transgenic mouse model of FAP was produced by microinjecting cloned human variant TTR gene into mice. Amyloid were demonstrated in thyroid, kidney and intestine and so on, but not in peripheral nerve in these mice. Pathogenesis of neuropathy of FAP is not known, but mechanical compression to the nerve, ischemia and metabolic abnormality may play some role combined to cause of nerve fiber damage. The effect of deposition on physiochemical functions of the neuron and mechanism to accumulate in nervous system of the TTR remain to be elucidated.