Abstract The Ig H chain locus is regulated by a set of cis-acting elements. Hypersensitive sites (HS) located 3′ of the IgH, HS1–4, has been suggested to act as a locus control region (LCR) in cell lines. To assess the proposed role of HS1–4 acting as an LCR, we generated transgenic mice harboring a VH promoter-β-globin reporter gene linked to the Ig H chain HS1–4 3′regulatory sequences. Transgene expression is strictly confined to B lymphocytes, with no detectable expression outside the B cell lineage in all transgenic founder lines. Furthermore, reporter gene activity is integration independent but not copy number dependent. Thus, additional sequences are required to allow the HS1–4 regulatory region to act as a classical LCR in mice. Our data are discussed in the context of tissue-specific gene expression in B lineage cells.