It has been well documented that transthyretin (TTR) shows an affinity for lipoproteins and amyloid is deposited around adipocytes in patients with familial amyloidotic polyneuropathy (FAP). We examined the involvement of lipids in amyloid fibrils in the tissues by histopathologic methods. Sudan black B staining for frozen tissues of autopsied FAP patients and biospied dialysis related amyloidosis (DRA) patients revealed colocalization of lipids in the tissue sections where Congo red staining was positive, while no such positive staining was observed in paraffin embedded tissues. Immunohistochemical study using lipoprotein antibodies revealed that only anti-high density lipoprotein (HDL) antibody showed immunoreactivity in both types of amyloid specimens where Congo red was positively stained. Measurement of the components of lipids in the frozen cardiac samples from an FAP patient and an amyotrophic lateral sclerosis (ALS) patient revealed that concentrations of triglyceride and cholesterol in each lipoprotein, except for HDL-triglyceride, were markedly elevated in the FAP patient's material, compared to that of the ALS patient. These results suggest that interaction of amyloid fibrils with HDL may play an important role in amyloid formation in FAP.