The Brn-3a and Brn-3b POU family transcription factors have previously been shown to have functionally antagonistic effects, with Brn-3a activating specific gene promoters which are repressed by Brn-3b. We show here that proliferating cell lines of human neuroblastoma origin have a high ratio of Brn-3b to Brn-3a compared with other cell lines derived from related tumours. Moreover, the level of Brn-3a rises and that of Brn-3b falls when neuroblastoma cell lines are exposed to treatments which induce a cessation of proliferation. Such treatments also result in the activation of a test promoter which is normally stimulated by Brn-3a and repressed by Brn-3b. Our findings suggest that these antagonistic factors may play a key role in regulation of gene expression during human neuroblastoma differentiation and could thus represent a potential therapeutic target for treatments designed to induce such differentiation.