A bleeding diathesis caused by platelet dysfunction is a major cause of morbidity and mortality in patients with uremia. Platelet adhesion to vascular subendothelium is defective in uremia and depends on the interactions of the platelet glycoprotein (GP) Ib/IX complex with the vascular wall. We measured levels of platelet surface GPIb, platelet surface GPIX, plasma glycocalicin (a product of enzymatic cleavage of GPIb), and ristocetin-induced platelet agglutination (RIPA) in patients undergoing chronic hemodialysis compared with patients undergoing peritoneal dialysis and healthy controls. Patients undergoing chronic maintenance hemodialysis have higher levels of platelet surface expression of GPIb (187+/-10 fluorescent units; P < 0.001) than either healthy controls (120+/-4 fluorescent units; P < 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P < 0.001). Similar changes were observed in platelet surface GPIX. Plasma glycocalicin levels were elevated in chronic hemodialysis patients (71+/-5 nmol/L) compared with healthy controls (36+/-3 nmol/L; P < 0.001). Plasma glycocalicin levels also increased progressively throughout the hemodialysis procedure. The slope of RIPA was significantly lower in chronic hemodialysis patients (46+/-3) than in either healthy controls (67+/-4; P < 0.05) or peritoneal dialysis patients (62+/-2; P < 0.05). In conclusion, patients undergoing chronic maintenance hemodialysis have increased plasma glycocalicin levels and decreased RIPA, which may contribute to diminished platelet adhesion to vascular subendothelium and increased bleeding associated with uremia.