Dialysis-related amyloidosis as represented by carpal tunnel syndrome is a serious complication of long-term dialysis treatment of patients with chronic renal failure. beta 2-microglobulin has been identified as a structural component of the amyloid deposits, but other factors also are associated with amyloid formation. We recently demonstrated the presence of apolipoprotein E and alpha 1-antichymotrypsin in the amyloid deposits. We therefore analyzed how polymorphic variants of both genes were related to the onset of amyloidosis. Among the apolipoprotein E genotypes, allele epsilon 2 represented a protective factor that delayed the onset of disease. In contrast, polymorphic alpha 1-antichymotrypsin alleles had no effect on the onset of amyloidosis. Thus, the apolipoprotein E epsilon 2 allele can be added to the list of factors that determine the onset of dialysis-related amyloidosis, which include patient age at initiation of dialysis therapy, dialysis duration, and the dialysis membrane used.