Platelet aggregation and interaction with other vascular cells play a key role in hemostatic events during hemodialysis. We studied seven patients with end-stage renal failure on long-term hemodialysis treatment. Flow-cytometric techniques and platelet-specific monoclonal antibodies were used to measure the platelet surface expression of glycoproteins-fibrinogen receptor on glycoprotein IIb-IIIa (GP IIb-IIIa; CD41) and alpha-granule membrane protein (GMP-140; CD62). In addition, adhesion of platelets or platelet microparticles with leukocytes was evaluated by appearance of the platelet-specific antigen (GP IIb-IIIa) on leukocytes. Blood samples were taken before the start of dialysis and 15, 60, and 240 min thereafter. There was a significant increase in fibrinogen receptor activation on circulating platelets after 15 min of dialysis treatment (P < 0.001) and enhanced degranulation of GMP-140 (P < 0.05). In parallel, the interaction of platelets with neutrophils and monocytes also increased with the duration of dialysis and was maximal after 15 min (P < 0.001). We conclude that the platelet fibrinogen receptor on GP IIb-IIIa in circulating platelets is activated during hemodialysis and is associated with increased adhesion of platelets or platelet microparticles with circulating leukocytes. Thus, the phenomenon described here of platelet-leukocyte interaction could be pathophysiologically important for the development of dialysis-associated leukopenia.