1. We have previously reported that the Na+ conductance in mouse intralobular salivary duct cells is controlled by cytosolic anions, being inhibited by high cytosolic concentrations of Cl- and NO3- but not of glutamate. In the present paper, we use whole-cell patch-clamp methods to investigate whether this anion effect is mediated by a G protein. 2. Inclusion of 100 mumol l-1 GTP-gamma-S, a non-hydrolysable GTP analogue, in the glutamate-containing pipette solution, i.e. when the Na+ conductance is active, reduced the size of the Na+ conductance whereas inclusion of 100 mumol l-1 GDP-beta-S, a non-hydrolysable GDP analogue, had no effect. 3. Inclusion of 100 mumol l-1 GDP-beta-S in the NO3(-)-containing pipette solution, i.e. when the Na+ conductance is inhibited, reactivated the conductance. Inclusion of 500 ng ml-1 activated pertussis toxin in the NO3(-)-containing pipette solution had a similar effect on the Na+ conductance. 4. We conclude that the inhibitory effect of intracellular anions such as NO3- and Cl- on the amiloride-sensitive Na+ conductance in mouse mandibular intralobular duct cells is mediated by a G protein sensitive to pertussis toxin.