Heteromultimeric cyclic nucleotide–gated (CNG) channels play a central role in the transduction of odorant signals and subsequent adaptation. The contributions of individual subunits to native channel function in olfactory receptor neurons remain unclear. Here, we show that the targeted deletion of the mouse CNGA4 gene, which encodes a modulatory CNG subunit, results in a defect in odorant-dependent adaptation. Channels in excised membrane patches from the CNGA4 null mouse exhibited slower Ca 2+ -calmodulin-mediated channel desensitization. Thus, the CNGA4 subunit accelerates the Ca 2+ -mediated negative feedback in olfactory signaling and allows rapid adaptation in this sensory system.