Extensive contact between blood and synthetic surfaces is associated with both quantitative and qualitative changes in platelet function. Cardiopulmonary bypass is associated with a decline in the circulating platelet count, release of platelet alpha granules and possibly platelet dense and lysosomal granule release, and a prolongation of the bleeding time. It is assumed that these platelet alterations contribute to postoperative blood loss and reoperation for bleeding. Improvements in technology have reduced but not eliminated the adverse platelet changes. Temporary inhibition of platelet function during surface contact has achieved additional improvement in the setting of heparin-induced thrombocytopenia but is not yet suitable for "routine" open heart surgery. Long-term cardiopulmonary bypass or extracorporeal circulation membrane oxygenation is receiving increased use during acute respiratory insufficiency. Systemic anticoagulation is required. Bleeding and platelet consumption continue as clinical problems and are treated by repeated platelet transfusion. Because no air interface is present in this setting and the synthetic surface is homogeneous this would appear to be the ideal area for application of platelet functional inhibition and synthetic surface passivation to reduce platelet consumption. Although still under review by the Food and Drug Administration, pulsatile devices, including the total artificial heart, increasingly are being used to provide temporary support for the failing heart. Furthermore, it is likely that totally implantable devices will become available in the very near future. Considering that thromboembolism is a major problem for recipients of mechanical valves, it is likely that thromboembolism will persist as a limiting factor in the further implementation of pulsatile devices. It is assumed that imaginative antithrombotic therapy will be required and that platelet activation will be fundamental to the thrombotic process. Platelet behavior in this setting, however, remains incompletely characterized. The analytical methodology that has been used to assess platelet behavior during cardiopulmonary bypass should be applied to the pulsatile devices as well and results correlated with clinical problems. This should permit standardization of antithrombotic therapy and rational use of platelet functional inhibition.