The anatomical and numerical simplicity of the fish olfactory system has led us to examine the family of olfactory receptors expressed in the catfish. We have identified a family of genes encoding seven transmembrane domain receptors that share considerable homology with the odorant receptors of the rat. The size of the catfish receptor repertoire appears to be far smaller than in mammals. Analysis of the nucleotide sequences suggests that these receptor genes have undergone positive Darwinian selection to generate enhanced diversity within the putative odorant-binding domains. Individual receptor clones anneal with 0.5%-2% of the olfactory neurons, suggesting that a single cell expresses only a small subset of distinct odorant receptors. Each cell, therefore, possesses a unique identity defined by the receptors it expresses. These data suggest that the brain may discriminate among odors by determining which neurons have been activated.