Transcriptional enhancers, originally discovered in viral genomes, are short, cis-acting, regulatory sequences that strongly stimulate transcription from promoters of nearby genes. We demonstrate the existence of an enhancer within a mouse immunoglobulin heavy chain gene. A DNA fragment located between the joining region and the switch recombination region in the intron upstream of the immunoglobulin mu constant region has been linked, in both orientations, to genes coding for rabbit beta-globin or SV40 T antigen. This element enhances the number of correct beta-globin gene transcripts by at least two orders of magnitude and also stimulates production of T antigen. It acts from several hundred to several thousand base pairs up or downstream of a promoter without amplifying template copy number. Of the various cell lines tested, the immunoglobulin gene enhancer functions only in lymphocyte-derived (myeloma) cells. We propose that this tissue-specific enhancer contributes to the activation of somatically rearranged immunoglobulin variable region genes and possibly to abnormal expression of other genes (e.g. c-myc) that become translocated to its domain of influence.