 Erythrocyte transfusions and hydroxyurea have many similar beneficial effects in patients with SCA. Transfusions may prevent primary stroke by lowering the HbS, by increasing the hematocrit, by improving red cell rheology, by decreasing red cell adhesion, and by lowering TCD velocity. Hydroxyurea leads to many of the same changes, thus in this protocol, we will examine whether hydroxyurea, like transfusions, can lower TCD velocity. In our patients with SCA who have been screened with TCD ultrasonography, we have observed that children who were screened while receiving hydroxyurea had lower TCD velocity measurements than those who were not on hydroxyurea. In a small number of patients with TCD velocity measurements before and after initiation of hydroxyurea for non-neurological reasons, the TCD velocity declined significantly after achieving full dose hydroxyurea therapy. The changes in TCD velocity were correlated with changes in hematocrit since hydroxyurea increases blood counts in patients with SCA. For each increase in hematocrit, the TCD velocity increased by 6.3 cmsec. This was similar to an abstract from the STOP trial, in which TCD flow velocity declined by 7.9 cmsec for each increase in hematocrit from transfusions. 