A monoclonal antibody (YK-2), which was previously established to react with apolipoprotein E (apoE) peptides in systemic amyloid deposits, was further characterized. Epitope of this antibody was determined to be the residue 221 to 230 of apoE. In comparison with polyclonal anti-apoE antibodies, this antibody showed strong reactivity with apoE peptides in amyloid fibril preparation but poor reactivity with native apoE protein or apoE in serum, indicating its usefulness for probing degraded apoE in amyloid deposits. Immunohistochemical studies resulted in strong reactivity for amyloid A and immunoglobulin light-chain deposits but weak for beta 2-microglobulin and beta amyloid (senile plaque) deposits. Although the association of apoE with amyloid is non-specific to the component peptide of amyloid fibrils, present findings suggest that the amount or degradation manner of apoE or the environment around the antibody epitope vary among types of amyloidosis.