In recent years prealbumin has been shown to be a major component of two forms of systemic amyloid, senile systemic amyloid (SSA), and familial amyloidotic polyneuropathy (FAP). Despite the fact that the amyloid fibril proteins associated with these two forms of amyloid, designated ASc1 and AF, respectively, share many similarities the clinical features of the two diseases are remarkably different. To understand better this paradox the clinical, histochemical, immunological and biochemical features of SSA and FAP were reviewed.