The early motion and interaction of platelets on a microdomain-structured block copolymer surface composed of 2-hydroxyethyl methacrylate (HEMA)-styrene were analyzed and compared with those on a compositionally identical random copolymer, homopolymer poly (HEMA) (hydrophilic) and polystyrene (hydrophobic) surfaces. Contacting platelets were quantitatively more active, with motions including rolling, detachment, oscillatory vibration, and change of direction only on the HEMA-St block copolymer surface. Active platelet movements were observed for long time periods (>20 min) on HEMA-St block copolymer surfaces and were distinct from those for inert PSt latex particles on these same surfaces, demonstrating that platelet movements were not due to physical forces such as convection, hydrophobic interactions, or microbrownian movement. To study the cause and mechanism underlying the platelet movements, platelets treated with an adenosine triphosphate (ATP) synthesis inhibition, NaN3, or a membrane skeleton-disrupting chemical agent, dibucaine, were also studied on these surfaces. Both treatments reduced platelet movement and demonstrated that platelets in contact with the HEMA-St block copolymer surface require metabolic processes consuming ATP and involve dynamics of their membrane skeleton. These energy-consuming active movements might explain the previously observed lower platelet activation and low thrombogenicity of the HEMA-St block copolymers. Enhanced platelet movements on the HEMA-St block copolymer surface show that the microdomain surface interacts uniquely with platelets to hinder activation and preserve passive platelet function despite surface contact.