The effect of nitric oxide (NO) on GABA induced Cl−current of recombinant GABAAreceptors was studied. Either α1β2γ2sor α1β2subunit mRNAs synthesized from cDNA of mouse brain were injected intoXenopusoocytes and functional GABAAreceptors were expressed. GABA-induced Cl−current was measured with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the GABA-induced Cl−current in the α1β2γ2ssubunit receptor in a dose-dependent manner. In α1,β2subunit receptor, NOC-18 had no effects on GABA-induced currents at low concentrations but showed potentiation at high concentration. These effects were antagonized by the NO extinguisher, carboxy-PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly acts at the GABAAreceptor and the γ2ssubunit is involved in its action.