beta-Thalassemia major (TM), a congenital hemoglobinopathy, is associated with hemodynamic disorders and with structural red blood cell (RBC) anomalies that may indicate impairment of RBC rheological properties. To gain insight into the possible contribution of RBC to the hemodynamic disorders, we studied RBC aggregability, which plays a central role in blood flow, particularly in the microcirculation. RBC aggregate size distribution and morphology of TM RBC were determined using a novel system for image analysis of blood cells in a flow chamber. It was found that the aggregability of RBC of TM patients is markedly enhanced. These cells form large clusters, as opposed to normal rouleaux, and higher shear stress is required to disperse them. The aggregate size of TM RBC is reduced to the normal range after the patients have received a blood transfusion. This study suggests that the hemodynamic disorders observed in TM may be linked to the enhanced RBC aggregability and that improvement of RBC rheological properties may be considered in the treatment of thalassemia.