The presence of point mutations at position -202 relative to the mRNA Cap site of both human fetalγ-globin genes is linked with elevated fetal globin levels in adults. The question addressed in this study is whether the -202 mutation affectsγ-globin gene expression in the same manner as the -117 hereditary persistence of fetal. hemoglobin (HPFH)Aγ-globin mutation. The -117 mutation was found to cause over-expression and confer inducibility of a retro-virally transferredγ-globin gene in cytosine arabinoside (araC)-treated KMOE cells in an earlier study. In this study, fetal globin genes driven by either the normalGγor -202 HPFHGγ-globin promoter were retrovirally transferred into human erythroid HOE cells. The -202 HPFH mutation did not cause over-expression or confer inducibility of the transferredγ-globin gene in araC-treated KMOE cells. Thus, the -202 HPFH mutation affectsγ-globin gene expression by a different mechanism than the -117 HPFH mutation. Furthermore, this study provides evidence against a general increasing ofγ-globin gene expression as might be expected from the -202 mutation altering binding of a ubiquitous factor such as Spl.