PURPOSE. Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk factors for this condition may be classified as genetic and environmental. Apolipoprotein E is putatively involved in the transport of the macular pigment (MP) carotenoids lutein (L) and zeaxanthin (Z) in serum and may also influence retinal capture of these compounds. This study was designed to investigate the relationship between macular pigment optical density (MPOD) and ApoE genotype. METHODS. This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. Serum L and Z were measured by HPLC. ApoE genotyping was performed by direct polymerase chain reaction amplification and DNA nucleotide sequencing from peripheral blood. RESULTS. Genotype data were available on 300 of the 302 (99.3%) subjects. The mean (± SD) age of the subjects in this study was 47.89 ± 11.05 (range, 21-66) years. Subjects were classed into one of three ApoE genotype groups, as follows: group 1, ε2ε2 or ε2ε3; group 2, ε3ε3; group 3, ε2ε4 or ε3ε4 or ε4ε4. All three groups were statistically comparable in terms of age, sex, body mass index, cigarette smoking, and dietary and serum levels of L and Z. There was a statistically significant association between ApoE genotype and MPOD. Subjects who had at least one ±4 allele had a higher MPOD across the macula than subjects without this allele (group 1 MPOD area, 0.70 ± 0.40; group 2 MPOD area, 0.67 ± 0.42; group 3 MPOD area, 0.85 ± 0.46; one-way ANOVA, P = 0.014. CONCLUSIONS. These results suggest that ApoE genotype status is associated with MPOD. This association may explain, at least in part, the putative protective effect of the ±4 allele for AMD and is consistent with the view that apolipoprotein profile influences the transport and/or retinal capture of circulating L and/or Z.