We measured the serum apolipoprotein levels in patients with familial amyloidotic polyneuropathy (FAP). The serum apolipoprotein AII levels were much lower than those of the control subjects, while the levels in asymptomatic carriers of the FAP gene were normal. Other plasma apolipoprotein levels, such as apolipoproteins AI, B, CII, CIII, and E, were all within normal ranges. The decrease of apolipoprotein AII in the plasma of FAP patients correlated with the progression of the disease. In a transgenic mice model of FAP carrying human variant transthyretin gene (Met-30), serum apolipoprotein AII levels were decreased in 1.5-year-old mice compared with control mice, while the 3-month-old mice had normal levels. These results suggest that apolipoprotein AII may play an important role in lipid metabolism or amyloid formation in patients with FAP.