A presumably spontaneous mutation has resulted in the formation of Hemoglobin (Hb) Istanbul in which glutamine is substituted for histidine in the proximal position of the beta-chain (F8(92)). The anemia and other physiological effects that occur in the presence of Hb Istanbul were much ameliorated by splenectomy. Hb Istanbul is a relatively unstable molecule which produces a rather moderate case of "unstable hemoglobin hemolytic anemia."In the determination of structure, a method of preferential cleavage of an aspartyl-proline bond at residues 99-100 of the beta-chain was used.