['Intravascular hemolysis releases large amounts of free hemoglobin (PFH) in plasma of sickle-cell disease (SCD) patients. PFH has been associated with harmful endothelial actions including scavenging nitric oxide (NO). Whether PFH plays a role in stroke in SCD has not been examined.', 'Serum levels of PFH, lactate dehydrogenase, and total bilirubin were measured in stored sera from children at risk for stroke treated in a randomized controlled trial of regular red cell transfusion (STOP study). Baseline and post-treatment (approximately 1 year of transfusion) were compared to determine whether treatment (which reduces stroke risk by 90%) was associated with reduction in markers of hemolysis.', 'Baseline serum PFH values did not differ between treatment groups. PFH declined with repeated transfusion from 78.7+/-8.2 mg/dL to 34.4+/-3.4 mg/dL (P<0.001). With only episodic or no transfusion the drop was smaller: 80.9+/-7.5 to 62.8+/-5.0 (P=0.019). The decrease was larger in those with regular transfusion (56% versus 22%; P<0.001). Reduction of lactate dehydrogenase and total bilirubin was observed only in those on regular transfusion.'] Does regular transfusion lower plasma free hemoglobin in children with sickle-cell disease at risk for stroke?