Brn-3a, Brn-3b and Brn-3c are closely related POU family transcription factors which are expressed predominantly in neuronal cells. Previously Brn-3a has been shown to activate a number of gene promoters in cotransfections carried out in different cell types, while Brn-3b inhibits the basal activity of these promoters. We show here that Brn-3c activates the same promoters as Brn-3a but only in co-transfections into neuronal cells and not in other cell types. This effect is dependent upon an N-terminal region of Brn-3c which acts as a neuronal cell specific activation domain when linked to a heterologous DNA binding domain. To our knowledge this is the first report of an activation domain with apparently neuronal specific activity.