Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and secondary pulmonary hypertension are common complications of sickle cell anemia. Pulmonary hypertension has now been identified as a major cause of death in adults with sickle cell disease. Similarly, pulmonary hypertension has been identified as a chronic complication of hemolytic disorders such as thalassemia, hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria. Sildenafil has been proposed as a possible therapy for both primary and secondary pulmonary hypertension and recent phase I/II studies from the intramural NIH suggest it is well tolerated and efficacious in this population. Furthermore, a number of recent studies have suggested that NO based therapies may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia.? ? This clinical trial is designed with three major objectives: 1) to assess cardiopulmonary function in patients with sickle cell disease and thalassemia with and without pulmonary hypertension, to better characterize the effects of chronic hydroxyurea therapy on cardiopulmonary function, 2) to determine the relative acute vasodilatory effects of sildenafil, and inhaled NO in patients with hemolysis-associated pulmonary hypertension and 3) to determine the chronic effects of the addition of inhaled NO on pulmonary hemodynamics and functional capacity in patients with hemolysis-associated pulmonary hypertension chronically treated with sildenafil. Male and female subjects, age 18 and above with sickle cell disease or thalassemia will be eligible for Stage I of the study. Stage I will evaluate up to 200 subjects and will include pulmonary function testing, chest x-rays, VQ scan, 6-minute walk, sleep study, cardiac MRI, MRI assessment of liver iron burden, high resolution CT scan, and blood tests. After the Stage I testing 50 subjects who are found to have mild to severe pulmonary hypertension will breathe nitric oxide for 20 minutes thourgh a facemask will undergoing the right heart catheterization. Then they will receive one dose of sildenafil and their pressures will be monitored for 4 hours followed by another 20 minutes of breathing nitric oxide. Stage III will be open to those individuals who have completed Stages I and II and have been on chronic sildenafil therapy for at least 3 months. Stage III consists of breathing nitric oxide through the INO Pulse device for 6 weeks while continuing to take the oral sildenafil therapy.