Activation of the retinoic acid receptor (RAR) beta 2 promoter is known to be mediated by a RA response element located in the proximity of the TATA-box. By deletion studies in P19 embryonal carcinoma cells we have analyzed the RAR beta 2 promoter for the presence of additional regulatory elements. We found that the cyclic AMP response element-related motif, TGATGTCA at position -99 to -92, is able to enhance RA-dependent RAR beta 2 promoter activation. In addition we demonstrate that this element, designated CRE-beta 2, is functionally active as a CRE since it can bind members of the CREB/ATF transcription factor family and, moreover, mediates the stimulatory effect of cAMP on RA-dependent RAR beta 2 promoter activation in human foetal kidney 293 cells.