11,129 individuals of the northern area of the island of Sardinia (7,717 newborns and 3,412 adults) were examined for the Hb G-Philadelphia variant [alpha 68(E17)Asn----Lys]. Hemolysates were analysed by isoelectric focusing, and the variant identified by reversed phase high performance liquid chromatography of tryptic peptides. A total of seven heterozygotes (1 in 1,589) were identified. This is probably the highest prevalence of this mutant so far described. Percentages of the variant (average 35.1 +/- 6.2%) were trimodally distributed with modes centering on 28, 36, and 42%, respectively. These values suggest that the G-Philadelphia allele occurs in Sardinians both on a single and on a double locus chromosome. The linkage with alpha-thalassemia may be the reason for the high frequency of the variant.