HbF was measured in the peripheral blood of 354 women during the first trimester of pregnancy. In those (n = 6) with HbF > 3% and in 30 randomly selected pregnant women with normal HbF values, analysis of the G gamma content and the Xmn I polymorphism was performed. The frequency of the Xmn I polymorphism was significantly higher (P < 0.001) in the group with high HbF (0.67) compared to the control group (0.10). The G gamma chain content evaluation revealed a newborn ratio in all 6 high HbF subjects. Six months after delivery, HbF was measured in all women with high HbF during pregnancy, revealing normal values. These results suggest that the presence of the Xmn I polymorphism is a strong inducer for the elevation of HbF during pregnancy.