s -chromosome haplotypes are peculiar to specific regions of Africa and Asia and are associated with the occurrence of different fetal hemoglobin (Hb) levels in sickle cell patients. Among these haplotypes,  s -chromosomes found in the Senegal and the Arab-India regions are associated with relatively high levels of HbF expression, whereas those around the Benin, Bantu, and the Cameroon regions show low levels of HbF expression. The roles of 5HS2 and the 5 flanking (promoter region) region in the expression of globin genes are well documented. Haplotype specific variations are found in these regions and have been postulated to be involved in the regulation of HbF expression. In this study, we have analyzed the effect of sequence variations in regulatory regions of the Bantu 5HS2 and 5 flanking region of the G ␥ gene on CAT expression. A diminution was observed in K562 cells when the promoter originated from the Bantu  s chromosome. The decreased expression was independent of the origin of the 5HS2 sequencecombinations of the Bantu promoter were measured with the Benin, Bantu, or Senegal 5HS2 sequences in K562 cells. However, expression of the same plasmids in murine erythroleukemic (MEL) cells showed no difference in CAT expression among the various sequence combinations studied. Am.