BACKGROUND: The apolipoprotein (Apo) E gene, and thus its gene product, plays a central and pervasive role in lipid metabolism by serving as a ligand for lipoprotein receptors. Polymorphisms of this gene have been associated with variation in lipid phenotypes in some Caucasian and Asian populations, but not in others. No such study has been carried out in a resident Irish population. AIM: A study was designed to examine the relationship between serum cholesterols and Apo E genotype in a cohort of healthy Irish adults. METHODS: One hundred healthy Irish adults, aged 19-65 years, were recruited from the Cork City area. Two fasting blood samples were collected from each subject. One was assayed for serum cholesterols--total and low-density lipoprotein (LDL), and high-density lipoprotein (HDL)--while the other sample was used for isolation of genomic DNA and determination of Apo E genotype. RESULTS: While the E2 (12%) was the least prevalent, E3 was the most prevalent Apo E genotype (66%) in this group of healthy Irish adults. A significant Apo E gene-dosage effect was evident, whereby individuals with the Apo E2 genotype had a lower level of total cholesterol, E3 had intermediate levels, and E4 had a higher level. Moreover, those with the Apo E4 genotype had a significantly higher level of LDL cholesterol compared to E2 or E3 genotypes. There was no significant difference in mean serum adjusted HDL-cholesterol levels between the three Apo E genotypes. CONCLUSION: These findings suggest that healthy Irish adults with the Apo E4 genotype have higher serum total and LDL-cholesterol levels than those with E2 or E3 Apo E genotypes and therefore may have a higher risk of atherosclerotic coronary artery disease and coronary heart disease in later life.