Thromboembolic complications associated with cardiovascular prostheses are thought to result from activation of coagulation factors or platelets by surface contact and/or by certain physical forces generated at the interface between the foreign material and blood. Studies of the effects on human platelets of one of these physical forces, shear stress, were made. A rotational viscometer was used to apply graded levels of shear stress to platelet-rich plasma. Very low shear stress (50 dynes per square centimeter) resulted in the liberation of small amounts of ATP, ADP, and serotonin and subsequent platelet aggregation. Stresses of 100 dynes per square centimeter or more resulted in the appearance in plasma of nonstorage nucleotides, indicating cell lysis, and shear stresses of 250 dynes per square centimeter or more resulted in the fragmentation of platelets. Shear-induced platelet aggregation was partially reversible but only those samples subjected to low levels of shear stress recovered their ability to aggregate to the subsequent addition of ADP. These studies indicate that platelets are extremely sensitive to shear stress and raise the possibility that thrombus formation and/or accelerated platelet turnover in patients with rheumatic valvular disease or who possess artificial heart valves or other cardiac prosthetic devices could result from the effects of this physical force on circulating platelets.