We have analysed the expression of cloned human fetal gamma-globin genes introduced into murine erythroleukemia cells by a protoplast fusion procedure. Both the wild-type a gamma-globin gene and a mutant derivative related to a phenotype of hereditary persistence of fetal hemoglobin were studied. In both cases the level of gamma-globin mRNA increased by a factor of approximately sevenfold when erythroid cell differentiation was induced by treatment with hexamethylenebisacetamide. Thus, the regulation of the expression of the cloned fetal A gamma-globin gene in murine erythroleukemia cells resembled that of cloned adult beta-globin genes.