We previously identified a novel orphan nuclear receptor referred to as NOR-1 from rat forebrain cells. This study examined the role of NOR-1 in primary cultured forebrain cells by selectively inhibiting NOR-1 expression by addition of antisense oligonucleotide to the culture media. Treating cells with the antisense oligomer resulted in the following dramatic morphological changes: (i) cell migration, (ii) extension of processes, and (iii) formation of cellular aggregates. Immunocytochemistry for microtubule-associated protein 2 revealed that the processes were filled with neurites growing from neuronal cells. These findings suggest that NOR-1 may be involved in the molecular mechanisms regulating neural differentiation.