Apolipoprotein E (ApoE) genotype influence on the relationship between dietary risk factors for cardiovascular disease and blood serum lipid levels was investigated in 132 free-living individuals participating in the European Prospective Investigation of Cancer (EPIC) study. All subjects (age 40-69) were clinically healthy and provided information on their usual diet. ApoE genotype and serum lipid concentrations were determined in all subjects. Relationships of intake of dietary constituents with serum lipid levels were compared in different genotype groups. There was a significant correlation between total serum cholesterol and intake of energy derived from total fat (r 0.195; P 0.025) and saturated fat (r 0.174; P 0.046) in the cohort as a whole. However, individuals with the ApoE epsilon3/epsilon4 genotype displayed a much stronger positive correlation between LDL cholesterol level and the percentage of energy derived from intake of saturated fat (r 0.436; P 0.043). There were no significant associations in the groups with epsilon3/epsilon3 or epsilon2/epsilon2 & epsilon2/epsilon3 genotype. A significant positive correlation between alcohol consumption and HDL cholesterol level was present in individuals bearing ApoE epsilon2 allele. These findings support current public health recommendations that saturated fat consumption should be reduced in order to reduce coronary heart disease risk. Total cholesterol concentrations were positively related to saturated fat intake in the cohort as a whole, but elevated LDL cholesterol levels associated with high saturated fat intake can be expected particularly in those individuals who combine a 'risky' dietary behaviour with the presence of the epsilon4 variant of ApoE.