Physicochemical characteristics of hydroxyethyl starch (HES) molecules determine their side effects on hemostasis. Our aim in the present experiments was to test the antiplatelet effect of novel high molecular weight HES. Citrated whole blood was hemodiluted in vitro (0% and 20%) with either HES 550 (Hextend(R)), HES 600 (6%Hetastarch-Baxter(R)), HES 200 (Elohast(R)), or the solvent of Hextend(R) in its commercially available solution. The availability of glycoprotein IIb-IIIa was assessed on nonstimulated and on agonist-induced platelets using flow cytometry. Glycoprotein IIb-IIIa availability increased significantly after hemodilution with Hextend(R) and its solvent by 23% and 24%, respectively, but decreased in the presence of 6% Hetastarch-Baxter(R) and Elohast(R) by 18% and 15%, respectively, with no significant difference between the latter two colloids. This study shows that Hextend(R) does not inhibit platelet function as anticipated by its high molecular weight and degree of substitution. The unexpected platelet stimulating effect of Hextend(R) is unique among the currently available HES preparations and may, at least in part, be induced by its solvent containing calcium chloride dihydrate (2.5 mmol/L). The platelet-inhibiting effect of 6%Hetastarch-Baxter(R) was not significantly different from that of medium molecular weight HES 200.