The expression of the endogenous CRF gene was examined in the human neuroblastoma cell line, BE(2)-M17. In this cell line, treatment with retinoic acid induces CRF mRNA transcription. We examined the requirement for the POU transcription factor, Brn-2, for this response. We confirmed that Brn-2 is expressed in retinoic acid-induced BE(2)-M17 cells. Expression of antisense Brn-2 message aborted the retinoic acid-mediated induction of CRF transcription. However, overexpression of Brn-2 was not sufficient for CRF expression in the absence of retinoic acid. These experiments support the hypothesis that Brn-2 is an intermediary for retinoic acid-induced CRF expression.