Macular degeneration associated with age and drusen, an important cause of visual loss, is associated clinically with alterations in the retinal pigmented epithelium. Because the pigmented epithelium is a copper-rich tissue with antioxidant properties, the copper economy in patients and controls were studied by measuring ceruloplasmin. Ceruloplasmin, a multifunctional, copper-binding alpha-globulin, was significantly elevated in non-related patients as compared with controls (691 +/- 153 mg/L vs 312 +/- 64; P less than .001), both by the p-phenylenediamine oxidation technique and radial immunodiffusion assay. When 53 members of a large family were divided clinically into persons with and without macular degeneration, the ceruloplasmin concentrations were not significantly different from each other, but were elevated as compared with non-related controls (P less than .001). These differences were not due to an intragroup age mismatch. A group of patients with retinitis pigmentosa had normal serum ceruloplasmin concentrations. This study suggests a relationship between serum ceruloplasmin, trace metals, and the tissue alterations associated with macular degeneration that deserves further investigation.