Fibulin-5 is an extracellular matrix glycoprotein that participates in elastogenesis. Mutations in the gene for fibulin-5 have been found to be associated with age-related macular degeneration. Little is known, however, about the expression of this gene in normal eyes or eyes with age-related macular degeneration. In this study, we evaluated the expression of the fibulin-5 protein in human donor eyes and localized this protein to Bruch's membrane and the intercapillary pillars of the choriocapillaris in normal eyes. In eyes with age-related macular degeneration, fibulin-5 was localized to pathologic basal deposits beneath the retinal pigment epithelium as well as some small drusen. These results suggest that fibulin-5 may promote extracellular deposit formation in macular degeneration.