The heterotrimeric G-protein G_s couples cell-surface receptors to the activation of adenylyl cyclases and cyclic AMP production (reviewed in refs , ). RGS proteins, which act as GTPase-activating proteins (GAPs) for the G-protein α-subunits α_i and α_q, lack such activity for α_s (refs ,,,). But several RGS proteins inhibit cAMP production by G_s-linked receptors^,. Here we report that RGS2 reduces cAMP production by odorant-stimulated olfactory epithelium membranes, in which the α_s family member α_olf links odorant receptors to adenylyl cyclase activation^,. Unexpectedly, RGS2 reduces odorant-elicited cAMP production, not by acting on α_olf but by inhibiting the activity of adenylyl cyclase type III, the predominant adenylyl cyclase isoform in olfactory neurons. Furthermore, whole-cell voltage clamp recordings of odorant-stimulated olfactory neurons indicate that endogenous RGS2 negatively regulates odorant-evoked intracellular signalling. These results reveal a mechanism for controlling the activities of adenylyl cyclases, which probably contributes to the ability of olfactory neurons to discriminate odours.