The ultrastructure of amyloid fibrils in familial amyloid polyneuropathy (FAP) was clearly demonstrated. Amyloid of three patients with FAP caused by the point mutation of the 30th amino acid of transthyretin (ATTR Val30Met) and one patient with FAP caused by two point mutations of the 30th and 104th amino acid of transthyretin (ATTR Val30Met/Arg104Cys) were partially isolated, stained negatively and examined with an electron microscope. Amyloid fibrils of both types were composed of two protofilaments and twisted at 180 degrees to the right and left alternately with a periodicity of 125-135 nm. This is the first report demonstrating such unique alternating twist structure of amyloid fibrils. There were no ultrastructural differences between the fibrils caused by the ATTR Val30Met and ATTR Val30Met/ Arg104His; therefore, it is suggested that the point mutation of the 30th amino acid of transthyretin might play an important role in the formation of amyloid fibrils. Further biochemical study on the mechanism of this alternating twist formation should be undertaken.