It has been demonstrated that the genetic polymorphism of apolipoprotein (apo) E is associated with atherosclerosis. Thus, in this study, we have examined the apo E allele frequencies in 109 patients with ischemic heart disease (IHD) and 576 Japanese people as controls, and we have compared these frequencies between patients with IHD and controls. The frequencies of the epsilon 2 and epsilon 4 alleles were significantly higher in patients with IHD than in the controls (epsilon 2: 8.2% vs 3.7%, epsilon 4: 17.0% vs 11.7%), whereas the frequency of the epsilon 3 allele was significantly lower in patients with IHD than in the controls (74.8% vs 84.6%). The epsilon 2-carrying patients with IHD were characterized by type III (43.8%) and IV (25.0%) hyperlipoproteinemia (HLP), whereas the epsilon 4-carrying patients with IHD were characterized by hypercholesterolemia (type IIb HLP: 42.8%, type IIa HLP: 28.6%). It is concluded that both epsilon 2 and epsilon 4 alleles are more associated with IHD than the epsilon 3 allele.