We have used a bespoke targeted mass-spectrometry assay to measure the circulating concentrations of all seven complement regulators and demonstrated elevated concentrations in 352 advanced AMD-affected individuals for all FHR proteins (FHR-1, p = 2.4 × 10−10; FHR-2, p = 6.0 × 10−10; FHR-3, p = 1.5 × 10−5; FHR-4, p = 1.3 × 10−3; FHR-5, p = 1.9 × 10−4) and FHL-1 (p = 4.9 × 10−4) when these individuals were compared to 252 controls, whereas no difference was seen for FH (p = 0.94). The gene discussed is CFHR3; the disease is age-related macular degeneration.