Inflammatory processes are implicated in the development and progression of age-related macular degeneration (AMD). However, there are limited data on longitudinal associations between systemic markers of inflammation and AMD. The authors examined the prospective relation between the circulating white blood cell (WBC) count and early and late AMD in a population-based cohort of 3,654 participants, aged 49-97 years, in the Blue Mountains region, Australia. The main outcome of interest was the 10-year incidence of early and late AMD among individuals free from corresponding disease at the baseline (1992-1994). An elevated baseline WBC count was associated with early AMD incidence, independent of smoking and other major confounders. The multivariable relative risk comparing tertile 3 of WBC count (>6.7 x 10(9) cells/liter) with tertile 1 (</=5.5 x 10(9) cells/liter) was 1.85 (95% confidence interval: 1.33, 2.58). The association between WBC count and early AMD was present consistently in analyses of different early AMD lesions, including incident pigmentary abnormalities and soft indistinct/reticular drusen. Moreover, this association persisted in subgroup analyses by gender and smoking. An elevated WBC count at baseline was not consistently associated with late AMD incidence. This study provides population-based evidence supporting a longitudinal association between the circulating WBC count, a widely available marker of inflammation, and incidence of early AMD.