AIM: To determine the sub-macular Bruch s membrane (BrM) macrophage count and the choroidal and BrM macrophage immunophenotype in normal eyes and in eyes with early and advanced age-related macular degeneration (AMD). METHODS: BrM macrophages were counted in 125 human eyes (normal, normal aged, early AMD and geographic atrophy) and CD68 and iNOS immunohistochemistry performed on 16 human eyes (normal, normal aged, early AMD, geographic atrophy and disciform scarring). All eyes were examined clinically ante mortem. Results were correlated with histopathological features, including basal laminar deposit and membranous debris, and with clinical fundus appearance. RESULTS: CD68+ macrophages were found in the choroid of normal human eyes, and did not express iNOS. Expression of iNOS by choroidal macrophages (as well as endothelial cells and pericytes) was associated with: (i) recruitment of macrophages to BrM in early AMD eyes with soft drusen or thick continuous basal laminar deposit (BLamD), corresponding to clinically detectable soft drusen or pigment changes; and (ii) active disciform scarring. iNOS expression was absent in BrM macrophages, suggesting immunomodulatory differences between the choroid and BrM. The highest BrM macrophage counts were found in eyes with subclinical CNV.