PURPOSE. To assess cross-sectional and longitudinal associations between exposure to Chlamydia pneumoniae infection and age-related macular degeneration (AMD) in the nested case-control sample drawn from the Blue Mountains Eye Study (BMES) cohort. METHODS. The BMES examined 3654 persons aged 49 to 97 years during 1992 through 1994 (BMES I survey). Survivors from this cohort (n = 2335; 75%) and 1174 persons who moved in this area or reached an eligible age were examined during 1997 through 2000 (BMES II survey, n = 3509). One hundred ninety-seven AMD cases and 433 control subjects matched for age, sex and smoking status, were drawn from the BMES II survey. Photographic macular grading followed the Wisconsin grading system. Plasma samples were analyzed with an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. Associations between seroreactivity to C. pneumoniae and prevalent and incident AMD were assessed by using logistic regression models. RESULTS. There were 159 early and 38 late AMD cases. Of them, 87 cases of early and 22 of late AMD developed between the baseline and follow-up examinations. After adjustment for age, gender, and smoking, no significant association was evident between C. pneumoniae antibody titer and any prevalent early or late AMD (OR 1.02, 95% CI 0.66-1.56 comparing upper with lower tertile of antibody titer). Findings were similar when early or late AMD was analyzed separately. Analysis confined to incident AMD also showed no significant association with the incidence of either early (OR 0.92, 95% CI 0.52-1.64) or late (OR 1.85, 95% CI 0.57-6.05) AMD. The results did not change after adjustment for family history of AMD and cardiovascular disease. CONCLUSIONS. In this nested case- control sample of an older Australian population we found no association between C. pneumoniae antibody titers and early AMD. The study has insufficient power to assess an association with late AMD.