Our previously published whole-cell patch-clamp studies on the cells of the intralobular (granular) ducts of the mandibular glands of male mice revealed the presence of an amiloride-sensitive Na+ conductance in the plasma membrane. In this study we demonstrate the presence also of a Cl- conductance and we show that the sizes of both conductances vary with the Cl- concentration of the fluid bathing the cytosolic surface of the plasma membrane. As the cytosolic Cl- concentration rises from 5 to 150 mmol/liter, the size of the inward Na+ current declines, the decline being half-maximal when the Cl- concentration is approximately 50 mmol/liter. In contrast, as cytosolic Cl- concentration increases, the inward Cl- current remains at a constant low level until the Cl- concentration exceeds 80 mmol/liter, when it begins to increase. Studies in which Cl- in the pipette solution was replaced by other anions indicate that the Na+ current is suppressed by intracellular Br-, Cl- and NO3- but not by intracellular I-, glutamate or gluconate. Our studies also show that the Cl- conductance allows passage of Cl- and Br- equally well, I- less well, and NO3-, glutamate and gluconate poorly, if at all. The findings with NO3- are of particular interest because they show that suppression of the Na+ current by a high intracellular concentration of a particular anion does not depend on actual passage of that anion through the Cl- conductance. In mouse granular duct cells there is, thus, a reciprocal regulation of Na+ and Cl- conductances by the cytosolic Cl- concentration.(ABSTRACT TRUNCATED AT 250 WORDS)