Previous studies have suggested that transcription of germline heavy chain constant region (CH)genes in murlne B cells may determine the potential of their different CH regions to undergo isotype switch recombination. We have examined the transcriptional activity across the immunoglobulin heavy chain (IgH) locus in human B lineage cells. Transcription of germline Cγ and Cα was observed in every surface lgM+ or surface lgM+/lgD+ B cell stage cell line and malignancy. In contrast, such transcription could not be detected in pre-B cells and only low levels of Cα but not Cγ transcription were evident in IgM-secreting plasmablast cells. Transcriptional activity of germline IgH Cε was singularly absent at all stages of B cell development. Our results suggest that germline transcription of the Cγ and Cα regions may be a constitutive feature of the human B cell differentiation program. Because this transcriptional activity is limited primarily to the B cell stage and occurs prior to the actual isotype switch, the induction of Cγ and Cα transcription may represent preparation of the downstream lgH chromatin for potential switch recombination. © 1991 Oxford University Press.