The contributions of particulate guanylyl cyclases to sensory signaling in the olfactory system have been unclear. This lecture will discuss the key findings that have reinvigorated the study of guanylyl cyclase function in mammalian olfaction. Studies of a specialized subpopulation of olfactory sensory neurons (OSNs) located in the main olfactory epithelium have provided novel insights into the neuronal function of one receptor guanylyl cyclase, GC-D. Gene-targeted mice expressing reporters such as beta-galactosidase and green fluorescent protein in OSNs that normally express GC-D have allowed us to identify these neurons in situ, facilitating anatomical and physiological studies of this sparse neuronal population. GC-D OSNs respond to a small group of chemostimuli including the natriuretic peptide uroguanylin, which is excreted into urine and feces, and the social odor carbon disulfide (CS₂), a component of rodent breath. Both molecules are detected at relatively low concentrations and require a cGMP signaling cascade that includes the cyclic nuceotide-gated channel CNGA3. The specific perturbation of signal transduction elements such as GC-D and CNGA3 indicates that neural activation of these cells is required for the acquisition of socially transmitted food preferences in freely behaving mice. Our results show that diverse activators of GC-D OSNs mediate social communication of food-related information and that genetic ablation of GC-D causes the loss of an associative olfactory learning that is essential in the acquisition of dietary preferences.