There are three major African haplotypes associated with the sickle mutation: Benin (#19), Senegalese (#3), and Central African Repblic (#20). Previous studies have suggested that the Xmn I site (-158 bp 5′to theGγgene) is associated with elevated levels ofGγandwiththe Senegalesehaplotype, while other investigators questioned this association. In order to clarify theissue.we have determinedβhalotypes, tested fortlie presenceof theXninI site, and measured HbF andGγexpressionlevels in 143 AmericanBlackpatients with sickle cell anemia. Haplotypes were determined using eight polvmorphic sites in theβ-like globin gene cluster: Hinc II 5′toϵ, Hind III in IVS-IIGγandAγ, Hinc II within and 3′toφβ, Ava II in IVS-II ofβ, and Hpa I and Bani HI 3′toβ. TheGγ/Aγratio was analyzed by high performance liquid chromatography using a C18column. The Xmn I site was present in all 31chromosomes with the Sengalese haplotype. Of the remaining 255 chromosomes with other haplotypes, only 2 (0.8%) had the Xmn I site present. Therewas significant correlation between the presence of the Xmn I site and increasedGγ/Aγratio in a dose-dependent manner.The Hb F level was not significantly, increased in thepresence of the Xmn I site.The data indicate that the Xmn I site maintains aGγ/Aγratio typical of fetal life but does not necessarily cause elevation of Hb F. The latter seems to depend on factors other than the Xmn I site.