Tissue accumulation of advanced glycation end-products (AGEs) has been implicated in the oxidant-induced vascular pathology of diabetes and other diseases. Because homozygous sickle cell anaemia (SCA) is a state of oxidative stress, we tested the hypothesis that circulating AGE levels are elevated in SCA. Blood was obtained from age- and race-matched children classified as either non-sickle cell controls, SCA without vaso-occlusive crisis (SCA - VOC), or SCA with vaso-occlusive crisis (SCA + VOC). Plasma and red blood cell (RBC) AGE levels were measured by immunoassay. RBC levels of reduced (GSH) and oxidized (GSSG) glutathione were measured by capillary electrophoresis as an indicator of endogenous antioxidant status. The results showed that plasma AGE levels and the rate of RBC AGE accumulation were significantly higher in patients with SCA compared with controls. GSH was not different between groups but was significantly inversely correlated with plasma AGEs in both controls and patients with SCA. GSSG was significantly lower and GSH/GSSG higher in SCA + VOC patients, suggesting that GSH/GSSG might be an objective indicator of acute VOC or a risk factor for VOC. We conclude that circulating AGE levels are strongly influenced by endogenous antioxidant status and may play a role in the vascular pathology of SCA.