The Olf-1/EBF (O/E) family of transcription factors plays important roles in neural development and B-cell maturation. We have utilized a variation of the direct selection scheme (Degenerate Oligo-based Direct Selection, or DODS) to identify a fourth member of the O/E family (O/E-4). We demonstrated that, similar to previously identified mouse O/E proteins, O/E-4 is expressed in the neuronal and basal cell layers of mouse olfactory epithelium. However, unlike other O/E members, O/E-4 expression is absent in the vomeronasal organ. O/E-4 can partner with the other O/Es to form heterodimers that are capable of binding an Olf-1 consensus site in vitro. In contrast to other O/E family members, the O/E-4 protein only weakly activates transcription in a reporter assay. In summary, we have identified O/E-4 utilizing a novel homology screening method. Our results suggest that O/E-4 may interact with other O/E family members to regulate gene expression in the olfactory sensory neurons.