Similar to the expression of antigen receptor genes in lymphocytes, the mammalian odorant receptor (OR) genes are expressed in a mutually exclusive and monoallelic manner in olfactory sensory neurons (OSNs). DNA rearrangement has long been regarded as a possible mechanism for the allelic exclusion of the OR genes. However, mice cloned from mature OSN nuclei expressed the full repertoire of ORs, and the possibility of irreversible gene translocation was excluded as a mechanism to activate a single OR gene in each OSN. How is allelic exclusion achieved in the olfactory system? Recent transgenic experiments indicated an inhibitory role of the OR protein in preventing further activation of other OR genes. Stochastic activation of an OR gene and negative-feedback regulation by the OR gene product might ensure the maintenance of the one neuron-one receptor rule in the mammalian olfactory system.