Isolated atrial amyloid (IAA) is a very common age-related amyloid form which is seen only in the atria of the heart. Chemical characterization has indicated that the major subunit protein is atrial natriuretic factor (ANF). In this ultrastructural study we show that the fibrils in IAA most frequently are located extracellularly especially along the cell membranes of the myocytes, but that small deposits also seem to be present intracellularly. No obvious relation was noted between the fibrils and the endocrine granules. Antiserum to a low molecular fraction of IAA labeled amyloid fibrils and granules in the same way as a commercial antiserum to ANF, but no other structures in the myocyte. Finally we show that ANF can polymerize to fibrils with an amyloid appearance. The study thus supports the fact that ANF is an important and integrated part in the IAA fibrils.