Genetic polymorphism of apolipoprotein E (apoE) is an important factor in the development of coronary artery disease but the results concerning apoE genotype and carotid artery atherosclerosis remain controversial. We investigated a random sample of 189 Finnish middle aged men (mean age 54 years, range 50-59) to assess the role of apoE in the process of carotid atherosclerosis. Intima-media thickness (IMT) of the carotid artery wall was measured at three standardised segments (common carotid artery, bifurcation and internal carotid artery) by B-mode ultrasonography. Overall mean IMT value was also calculated. The carriers of E3/2 (n=20) genotype had significantly lower (P<0.01) total cholesterol and LDL cholesterol concentrations than carriers of E3/3 genotype (n=109) or the E4 allele (n=60). ApoE polymorphism was associated with common carotid artery IMT (P=0.034) when adjusted for age and body-mass index (model 1). The carriers of E3/2 had on average 9% (95% CI 0.8-16%, P=0.028) lower common carotid IMT values than the carriers of E3/3. After further adjustment with LDL and HDL cholesterol, systolic blood pressure, lipoprotein (a), apolipoprotein B and pack-years of smoking (model 2) the association was not statistically significant. The overall mean IMT varied significantly with apoE genotype (P=0.03 for model 1 and P=0.07 for model 2), and it was also lowest in the carriers of E3/2 genotype. This suggests that apoE E3/2 genotype is a protective factor in the development of carotid artery atherosclerosis in randomly selected middle-aged men. The favourable effect might be mediated at least partly by the lowering effect of E3/2 genotype on serum cholesterol.