In order to clarify the pathology of familial amyloidotic polyneuropathy, 9 autopsy cases and 5 biopsy cases of the disease occurring in Arao city of the Kumamoto Prefecture, Japan, were examined pathologically, histochemically, immunohistochemically and electron microscopically. The autopsy cases were 4 males and 5 females, and their age of death ranged from 36 to 56 years (45.2 years in average). Biopsy was performed from the sural nerves in 4 males and one female of the same families at the age of 26 to 48 years (39.6 in average). In the autopsy cases, amyloid deposition was marked in the peripheral nerve tissues, choroid plexuses, cardiovascular system, kidneys and thyroid. In the cardiovascular system, amyloid favorably deposited in the wall of small blood vessels, particularly arteries, and in their surrounding tissues. In the cardiac conduction system, the sinoatrial node and both bundle branches were severely affected, accompanied by amyloid deposition, whereas the atrioventricular node and His bundle were less involved. In the sural nerves of the biopsy cases, degenerative changes corresponding in degree to the duration of their clinical course were observed particularly in the endoneurium and amyloid deposition occurred around the blood vessels. On electron microscopy, degenerative changes were confirmed in the axon, myelin sheath and Schwann cells, accompanied by irregularity of the cytoplasmic processes, increased numbers of collagen fibers and regeneration of myelinated nerve fibers. The morphometric study showed decreased numbers of small-calibred myelinated fibers during the early stage. In the kidneys, amyloid deposition was found in almost all the glomeruli and diffusely around the renal tubules. However, amyloid deposition in the liver, bone marrow, lymph nodes or central nervous system were less marked. Histochemically, the amyloid deposits were resistant to KMnO4 treatment in Congo red stain, and immunohistochemistry demonstrated the amyloid precursor protein to be prealbumin.