This is a Phase III randomized clinical trial for children with SCA. The hypothesis is that hydroxyurea and phlebotomy can maintain an acceptable stroke recurrence rate and significantly reduce the hepatic iron burden. The primary aim is to compare standard therapy (transfusions and chelation) with alternative therapy (hydroxyurea and phlebotomy) for the prevention of secondary stroke and management of iron overload. Additional aims include comparisons of growth and development, frequency of non-stroke neurological and other sickle-related events, and quality of life. The use of hydroxyurea for secondary stroke prevention, coupled with removal of excess iron by phlebotomy, would represent a significant improvement in the management of individuals with SCA and stroke. If hydroxyurea is effective for the prevention of secondary stroke, it may also be beneficial for other children with SCA and cerebrovascular disease, including those at risk for primary stroke.