The mutation of serine128 to arginine in the CD 62E gene is a risk factor for coronary artery disease (CAD). We designed a new method to detect this mutation based on the observation that it is due to a transversion of nucleotide A561 to C, which abolishes a PstI recognition site. Two alleles, A and C, are easily typed when genomic DNA is amplified by PCR, digested with PstI, and separated on agarose gels. Among 153 people who underwent an elective, diagnostic arteriography in Johns Hopkins Hospital, we found that the C allele accounts for 19.5% in angiographically documented CAD patients (n = 82). It is significantly higher than the 10.6% frequency observed in normal controls (n = 71, p < 0.05). It indicates that the C allele is associated with early-onset CAD. This new method should facilitate the screening of this mutant allele in large populations and contribute to the understanding of the molecular mechanism underlying the association of this mutation with CAD.