Human δ globin is expressed at approximately 1–2% of the level of human β globin in erythroid cells despite the marked homology between these two globins. To determine the DNA sequences responsible for this effect, δ and β globin genes and fusion products of these genes constructed in vitro were transfected and expressed in HeLa cells. The results indicate that when the small intervening sequence of the β gene (β IVS 1) is replaced by β IVS 1, expression of the chimeric gene is the same as that of the normal β globin gene. By contrast, when the large intervening sequence of the β gene (β IVS 2) is replaced by δ IVS 2, expression of the chimeric gene is markedly reduced. These results suggest that there are signals within IVS 2 of the δ and β genes which affect their relative expression.