We present a modification to the polymerase chain reaction amplification/Hhal restriction isotyping method for human apolipoprotein (apo) E. This method includes a mutagenic forward primer and 5'-end labeling of both primers. These modifications of the original method described by Hixon and Vernier (J Lipid Res 1990;31:545-8) allow sensitive and unambiguous determination of apoE genotypes.