We introduced into MEL cells rabbit/3-globin gene deletion mutants and two sets of hybrid genes constructed from the inducible human@-globin gene and noninducible human y-globin gene or the murine H-2K”‘“’class I MHC gene. Sl nuclease analysis of gene transcripts before and after MEL differentiation showed that induction of the rabbit@-globin gene did not require more than 58 bp of DNA 5’to the transcription initiation site. Hybrid genes were constructed with human B-globin DNA sequences from either 5’or 3’of the translation initiation site linked to the complementary parts of the-y or H2Kbm’genes. Both types of constructs were inducible during MEL differentiation. The relative rates of transcription of the 5’7-3’8 and 5’H2-3’8 hybrid genes show that induction of the hybrid gene transcripts results at least in part from transcriptional activation of the genes. We suggest that DNA sequences that regulate 8-globin gene transcription during MEL differentiation are located both 5’and 3’to the translation initiation site.