The amino acid substitution (B Glu → G6 Val) results in the conversion of Hemoglobin A (HbA) to sickle cell hemoglobin(HbS) which is responsible for sickle cell disease. Under physiological conditions this substitution causes a reduction of the solubility of HbA from about 340 mg/ml to 165 mg/ml (for HbS). One consequence of the reduction in solubility is that HbS polymerizes to form long fiber like structures about 240Å in diameter. The formation of these fibers causes sickle cell disease. The fibers fill the red cell and cause it to assume a characteristic sickle shape. More significantly the fibers cause the red cell to become rigid and, as a result, sickled cells can block blood flow in the capillaries. Understanding the polymerization process in detail is important for understanding the pathophysiology of sickle cell disease and for developing a specific therapy that could be used in its treatment.