OBJECTIVE: Recent evidence suggests an important role for the complement system in the etiology of age-related macular degeneration (AMD). We aimed to investigate whether other diseases known to be associated with complement activation are associated with AMD. DESIGN: Case-control study. PARTICIPANTS: We reviewed medical records from the United Kingdom General Practice Research Database (GPRD). Cases (n = 18 007) were defined as people aged >/=50 years with a first diagnosis of AMD while registered with a practice included in the GPRD between 1987 and 2002. For each case, 5 controls with no record of AMD (n = 86 169) were matched by gender, practice, and age (within 5 years). METHODS: Records were searched for diagnoses of systemic lupus erythematosus (SLE), glomerulonephritis, and diabetic nephropathy occurring before the AMD diagnosis date (or equivalent date for controls). MAIN OUTCOME MEASURES: Diagnosis of AMD. RESULTS: A diagnosis of SLE was found in 0.07% of controls and 0.13% of AMD cases (confounder-adjusted odds ratio [OR], 1.69; 95% confidence interval [CI], 1.05-2.72). Glomerulonephritis was diagnosed in 0.13% of controls and 0.2% of cases (adjusted OR 1.46; 95% CI, 0.99-2.13). Diabetic nephropathy was strongly associated with AMD with an adjusted OR of 3.00 and a 95% CI of 1.55-5.97, which was independent of the association of diabetes with AMD. CONCLUSIONS: Specific diseases that are associated with complement activation are also associated with AMD. The impact of diabetic nephropathy on AMD may be larger than previously recognized.