The neuronal nicotinic acetylcholine (nACh) receptor is one of the ligand-gated ion channels that regulate the synaptic release of neurotransmitters in the central nervous system. Recently, neuronal nACh receptors have received attention as a potential target for general anesthetics because many general anesthetics inhibit their functions at clinical concentrations. Several general anesthetics are known to inhibit the homomeric (alpha(7))(5) nACh receptor, a subtype of neuronal nACh receptors, but the effects of two gaseous anesthetics, nitrous oxide (N(2)O) and xenon (Xe), remain unknown. Using the two-electrode voltage-clamping technique, we investigated the effects of N(2)O and Xe at the human (alpha(7))(5) nACh receptor expressed in Xenopus oocytes. At clinically relevant concentrations, N(2)O and Xe reversibly inhibited the ACh-induced currents of the (alpha(7))(5) nACh receptor in a concentration-dependent manner. The inhibitory actions of both anesthetics at the (alpha(7))(5) nACh receptor were noncompetitive and voltage-independent. Our results suggest that inhibition of the (alpha(7))(5) nACh receptor by N(2)O and Xe may play a role in their anesthetic effects.