PURPOSE: To examine the association of systemic markers of inflammatory disease and endothelial dysfunction with age-related maculopathy (ARM). DESIGN: (1) Nested case-control analysis of prevalent ARM and (2) prospective analyses of incident ARM in a random sample of a population-based cohort. METHODS: Standardized protocols for blood collection, measurement of markers, administration of a questionnaire, and gradings of stereoscopic color fundus photography to determine ARM were used. Standard univariate and multivariate analyses were performed. participants: Included in the nested case-control study were 188 cases with moderate to advanced ARM and 195 controls matched for age, gender, and current smoking status at a baseline examination from 1988 to 1990, and living in Beaver Dam, Wisconsin. Included in the prospective analyses as a random sample of 321 persons were those who participated in a 5-year and/or 10-year follow-up. main outcome measures: Prevalent and incident ARM. RESULTS: Serum C-reactive protein, amyloid A, interleukin-6, tumor necrosis factor-α, intracellular adhesion molecule, E-selectin, folate, and Chlamydia pneumoniae IgG antibody were not associated with either prevalent or incident ARM. CONCLUSION: Contrary to other reports, we cannot confirm a strong or consistent relationship of markers of inflammation and endothelial dysfunction with ARM.