Studies have identified apolipoprotein E (apoE) ubiquitously in biochemically distinct amyloid deposits including amyloid A protein (AA) in secondary amyloidosis and amyloid beta protein (A beta) amyloid in Alzheimer's disease (AD). Apolipoprotein A-1 (apoA-1) has been identified in cortical plaques derived from the tissues of patients with AD. To determine if apoE is essential for and apoA-1 may be a factor in AA-amyloidogenesis we investigated induction of secondary amyloidosis in mutant C57BL/6J mice that lack either apoE or apoA-1. Induction of secondary amyloidosis in nonmutant C57BL/6J mice that are AA amyloid-susceptible were the AA positive control. Discreet deposits of AA amyloid were detected in the perifollicular regions of spleens derived from mutant and nonmutant strains. The findings clearly demonstrate that generation of AA fibrils can occur independently of apoE and ApoA-1 expression.