The sickle cell disease that occurs in the Eastern Province of Saudi Arabia is reported to be clinically benign. It is biochemically characterized by high levels of fetal hemoglobin. Twenty-four Saudi patients with sickle cell disease were compared with 22 American patients. As a group, the Saudi patients were less anemic and had less hemolysis, microcytic RBC, and much higher levels of Hb F. Splenic function was assessed by enumeration of pocked RBC. Seventeen Saudi patients had low numbers of Pk RBC, indicating normal or nearly normal splenic function, whereas all American patients had markedly decreased splenic function and high numbers of Pk RBC. Low levels of Pk RBC were strongly associated with high levels of Hb F. The genetic basis of the milder sickle cell disease in Saudi Arabia has not been elucidated, but may involve multiple genetic factors. Although the sickle cell disease in Arab patients of eastern Saudi Arabia is often less severe than that in America, it is far from "benign," and some patients have severe clinical courses similar to those in patients in the West.