Erythrocytes (RBCs) from six patients with sickle cell anemia were transfused to laboratory rats in order to study the intravascular survival of irreversibly sickled cells (ISCs). Fifteen minutes after transfusion, a mean of 48.8 percent (range 23-95 percent) of the ICSs injected were present in the rats' blood, a value that was significantly lower than that for the total population of sickle cell anemia erythrocytes transfused (mean 82.4 percent, range 36-114 percent). The intravascular half-life of ISCs was also lower (mean 0.83 hours ± 0.18 SD) than that observed for the total sickle cell anemia erythrocytes (mean 1.62 hours ± 0.19 SD) during the initial two hours of the transfusion experiments. The irreversibly sickled cells that remained in the rats' blood thereafter survived as well as those cells that were not irreversibly sickled. Severe hypoxia in the recipient animals did not appear to selectively remove ISCs from circulation. These data are consistent with heterogeneity of ISCs in terms of their intravascular viability. Some ISCs may have adapted to the stress of circulation despite their abnormal shape.