The dunce (dnc) gene in Drosophila codes for a cyclic adenosine monophosphate-specific phosphodiesterase (PDE). Flies with a mutation at this locus exhibit severe deficits in learning and memory. We have begun to analyze the neural distribution of mammalian homologs of dnc in the mouse. Surprisingly, in situ hybridization and northern blotting using a probe specific for one of the four mammalian dnc homologs (mPDE2) reveals high levels of expression in the olfactory neuroepithelium. Anti-mPDE2 antibody confirms that this PDE protein is abundant in the axons and dendrites of the olfactory receptor neurons but is conspicuously absent from the cilia, where the initial events in olfactory signal transduction occur. Lower levels of mPDE2 were also detected throughout the brain and in the testis. These findings suggest an important modulatory role for mPDE2 in mammalian olfaction.