Therapeutic plasmapheresis has been recommended as the choice therapy in patients with familial hypercholesterolemia. Little is known about the effect of plasmapheresis on platelet behavior. By means of electron microscopy we have studied the platelet plasma membrane of 4 patients with familial hypercholesterolemia who were submitted to repeated plasmaphereses. After each procedure of plasmapheresis, at the 15th day, morphometrical studies revealed a statistically significant increase in the surface density of the Open Canalicular System, which is considered a marker of platelet activation. However, during 12 months of plasmapheresis, a significant mean decrease in the morphometric parameters was observed. On one hand, these results indicate the necessity to consider the blood hemocoagulatory state in the patient who has been submitted to the above mentioned treatment, since the variation of these parameters after the therapeutic procedure, in a short time, could be potentially harmful to the patient; on the other hand, these results indicate, for the first time, the ability of the procedure to improve platelet behavior after repeated treatments on long term basis.