On the basis of STOP II, even those whose risk of stroke decreases with transfusion therapy on the basis of TCD criteria have an 50% probability of reverting to high risk or having a stroke if transfusion therapy is discontinued. Alternative methods of maintenance therapy that are safer than transfusion need to be developed because studies show the need for ongoing active treatment despite TCD normaliza- tion and the risk of iron toxicity with repeated transfusions. Predictive methods other than TCD (eg, MRI techniques) need to be systematically compared and combined with TCD to further refine the estimation of stroke risk in individuals. Hydroxyurea may be beneficial when red cell transfusions are not feasible but should not be considered as a substitute for transfusion. Data on risk of stroke and prevention options in adults with SCD are needed, and a stroke prevention strategy for adults needs to be developed. Future stroke prevention tri- als are needed for adults with SCD. SCD: Recommendations 1. TCD screening for children with SCD is indicated starting at 2 years of age and continuing annually to 16 years of age (Class I; Level of Evidence B). 2. Transfusion therapy (target reduction of hemoglobin S, <30%) is effective for reducing stroke risk in those children at elevated risk (Class I; Level of Evidence B). 3. Although the optimal screening interval has not been established, it is reasonable for younger children and those with borderline abnormal TCD velocities to be screened more frequently to detect the development of high-risk TCD indications for intervention (Class IIa; Level of Evidence B). 4. Pending further studies, continued transfusion, even in those whose TCD velocities revert to normal, is probably indicated (Class IIa; Level of Evidence B). 5. 