Over the past year, substantial progress was made toward understanding transcriptional control of red cell differentiation. Complementary DNAs encoding two novel erythroid-restricted transcription factors--globin locus control region regulatory factor NF-E2 and CACC-binding protein EKLF--were cloned and characterized. Other DNA-binding activities have been implicated in developmental regulation of hemoglobin expression; these are postulated to mediate competitive interactions between globin gene promoters. As individual transcriptional regulatory factors are better understood, attention must turn to how they interact among themselves and with other proteins to initiate and maintain the erythroid program.