We have carried out a mutational analysis of the mouse IgH enhancer. Consistent with previous reports, deletions extending from either the 5' side or the 3' side of the enhancer fail to reveal distinct boundaries which define enhancer function in lymphoid cells. Interestingly, internal point mutations and deletions within the "enhancer core" regions fail to identify any necessary functional role for these conserved elements. When tested in CV1 cells, which do not normally respond to the IgH enhancer, certain deletions exhibit significant enhancer activity. We take these findings to indicate that the functional domains of the IgH enhancer are complex and that cell type specificity is defined in part by negative factors present in non-lymphoid cells.