Intravascular thrombus formation downstream of cerebral arterial occlusion may result in necrosis of ischemic tissue. To clarify the causative mechanisms, interaction between adenosine-5'-diphosphate (ADP)-activated platelets and cultured human aortic endothelial cells (HAEC) was examined by employing video enhanced contrast-differential interference contrast (VEC-DIC) microscopy. The numbers of (1) control/platelets, (2) ADP-activated platelets, (3) ADP-activated, anti-platelet GP Ibalpha antibody (GUR20-5)-treated platelets, and (4) ADP-activated, platelet GP IIb/IIa antagonist (TAK-029)-treated platelets, associated with HAEC after superfusion and wash-out were counted in visual fields of 30 x 30 microm2. Many ADP-activated platelets adhered to HAEC directly, while almost no platelets adhered to HAEC in the control. The adhesion was almost completely blocked by the GP IIb/IIIa antagonist, but not by GP Ibalpha antibody. We conclude that initial binding of ADP-activated platelets to HAEC is mediated by platelet GP IIb/IIIa in this in vitro system.