A longitudinal, prospective, controlled evaluation of magnetic resonance images (MRI) of long bones in sickle cell patients was undertaken simultaneously with assessment of clinical status and hematologic parameters, including dense erythrocytes. MRI of bone marrow in sickle cell patients during steady states appeared patchy and were markedly different from those in matched controls (P approximately 0). Patients with severe patchiness were older than those with mild or moderate patchiness (P less than .03). Sixty-nine MRI were performed during 28 painful episodes occurring in 14 subjects with sickle cell disease (SCD). Increased signals on intermediate and T2-weighted images were detected in 35.7% of painful episodes. These abnormalities were distinct and not observed to occur spontaneously during the steady- state examinations (P approximately 0). Bone marrow infarcts were confirmed by biopsy in two instances and autopsy in one instance. Dense red cells decreased by 40.81% of baseline during pain crises (P = .00005), more remarkably in those who had pain in the lower extremities (P = .0145). Patients with change in MRI during pain crises had a greater percentage change in the dense cells than those without the change in MRI (69.7% v 31.3%, P = .0120).