Mammalian olfactory sensory neurons harbor a large repertoire of odorant receptors. Yet, each cell chooses a single odorant receptor gene to express, which may then serve as the molecular identification of that cell. This process of differentiation or receptor gene regulation of olfactory sensory neurons has largely been enigmatic. Here, we showed that the important proto-oncogene in B lymphocyte terminal differentiation, B-Cell Leukemia/Lymphoma 6 (BCL-6), which codes for a sequence-specific transcription repressor, is expressed in olfactory sensory neurons in the mouse. We detected BCL-6 mRNA in most, if not all, mature olfactory sensory neurons by in situ hybridization histochemistry. Western blot analysis also revealed the presence of BCL-6 protein in the olfactory epithelium, but immunohistochemical analysis using anti-BCL-6 antibodies showed that only a subset of olfactory sensory neurons highly expressed BCL-6 protein. BCL-6 mRNA was detected as early as embryonic day 14 (E14) in most olfactory sensory neurons as in adults, and at E15, BCL-6 protein was detected in most cells that were likely to be differentiating into mature olfactory sensory neurons. Artificial induction of apoptosis of olfactory sensory neurons resulted in the decrease of BCL-6 mRNA, but during the subsequent phase of regeneration and differentiation, it markedly increased. Taken together, our results suggest the possibility that BCL-6 plays an important role in terminal differentiation not only in B lymphocytes but also in olfactory sensory neurons.