Pseudoexfoliation syndrome (PEX) is a systemic disorder characterized by the deposition of an abnormal fibrillar material in ocular and various extraocular tissues. It represents the most common identifiable cause of glaucoma (PEX glaucoma = PEXG). Due to similar pathogenetic mechanisms, glaucoma has been called "ocular Alzheimer's disease". PEXG and Alzheimer's disease share common associations such as the higher prevalence of hyperhomocysteinemia in both disorders. In order to investigate the cause of hyperhomocysteinemia in PEXG, we evaluated B-vitamin levels (folate, B12, B6) and their associations with homocysteine (Hcy) in plasma of 70 PEXG patients and 70 control subjects. Folate, vitamin B12 and B6 levels were significantly decreased and associated with elevated Hcy levels in PEXG. Low B-vitamin levels in PEX might also help explain, at least in part, the higher prevalence of B-vitamin deficiency in disorders associated with PEX such as Alzhemier's disease.