As many as 7,717 babies born consecutively and 3,412 blood donors of Sardinian ancestry have been examined for the detection of the Hb J-Sardegna variant [alpha 50(CE8)His----Asp]; all subjects were from Northern Sardinia. Hemolysates were analyzed by isoelectricfocusing and the identification of the variant was made by reversed phase high performance liquid chromatography of the tryptic peptides. A total of 28 carriers (1:397) of Hb J-Sardegna were identified. The incidence of 0.25% makes this hemoglobin one of the most common alpha-globin structural mutants in humans. The distribution of the anomaly appears to be nonhomogeneous in the island. The quantity of the variant ranged from 19 to 36%; this wide range probably reflects the co-inheritance of an alpha-thalassemia anomaly.