A fundamental belief in the field of olfaction is that each olfactory sensory neuron (OSN) expresses only one odorant receptor (OR) type. Here we report that coexpression of multiple receptors in single neurons does occur at a low frequency. This was tested by double in situ hybridization in the septal organ in which greater than 90% of the sensory neurons express one of nine identified ORs. Notably, the coexpression frequency is nearly ten times higher in newborn than in young adult mice, suggesting a reduction of the sensory neurons with multiple ORs during postnatal development. In addition, such reduction is prevented by four-week sensory deprivation or impaired apoptosis. Furthermore, the high coexpression frequency is restored following four-week naris closure performed in young adult mice. The results indicate that activity induced by sensory inputs plays a role in ensuring the one cell-one receptor rule in a subset of olfactory sensory neurons.