Age-related macular degeneration is the most frequent cause of blindness in the elderly. A vascular basis of the disease has been suggested, but not confirmed. The association between atherosclerosis and this type of macular degeneration was investigated in 104 subjects with and 1,324 subjects without macular degeneration as part of the population-based Rotterdam Study. The study was performed between March 1990 and July 1993 in a suburb of Rotterdam, the Netherlands. Macular degeneration was assessed on fundus photographs. Carotid atherosclerosis was ultrasonographically evaluated by measurement of the common carotid intima-media thickness and by assessment of the presence of atherosclerotic plaques. Atherosclerosis in arteries of the lower extremities was studied by determination of the ankle-arm systolic blood pressure ratio. In subjects younger than age 85 years, plaques in the carotid bifurcation were associated with a 4.7 times increased prevalence odds of macular degeneration (95% confidence interval (CI) 1.8-12.2); those with plaques in the common carotid artery showed an increased prevalence odds of 2.5 (95% CI 1.4-4.5). The intima-media thickness of the common carotid arteries was not significantly different. Lower extremity arterial disease (ankle-arm index less than 0.90 on at least one side) was associated with a 2.5 times increased prevalence odds (95% CI 1.4-4.5). These findings suggest that atherosclerosis may be involved in the etiology of age-related macular degeneration.