Apolipoprotein E is commonly present in systemic amyloid deposits. To investigate the possibility of using apolipoprotein E immunotargeting in the diagnosis and treatment of amyloidosis, we examined whether anti-apolipoprotein E monoclonal antibody was bound to murine amyloid deposits in vivo and whether it influenced amyloidogenesis. This study utilized a radiolabeled monoclonal antibody specific to human apolipoprotein E fragments and human apolipoprotein E-knock-in mice, in which AA amyloidosis was induced. Accumulation of the injected radiolabeled antibody was significantly higher in the organs of amyloidotic mice than in those of non-amyloidotic mice. Plasma clearance of the antibody did not differ between the amyloidotic and non-amyloidotic mice. The antibody was given to mice during amyloid induction but failed to prevent amyloidogenesis. The results of this initial study are encouraging, but considerable improvement is necessary, particularly in regard to development of a high affinity antibody.