We evaluated the activation and destruction of platelets in 24 patients with rheumatic heart disease (RHD) involving the mitral valve. Ex vivo platelet aggregation induced by adenosine diphosphate (ADP) and collagen was significantly increased in RHD patients as compared with normal controls. Plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 were also elevated. Plasma concentrations of glycocalicin, a proteolytic fragment of platelet membrane glycoprotein Ib, were increased, while platelet counts were decreased in RHD patients as compared with normal controls. RHD patients with, versus those without, atrial fibrillation demonstrated significant differences in beta-TG levels and platelet counts. However, we observed no difference in glycocalicin levels between the two groups. The present study demonstrated that increased platelet activation, as well as platelet destruction, occur in patients with RHD.