Exposure of Xenopus laevis oocytes to NH(4)Cl caused intracellular acidification, cell membrane depolarization and the generation of an inward current. To determine the contribution of uncharged NH(3) and positively charged NH(4)(+), the NH(4)Cl-induced inward current was measured in the presence of increasing [NH(3)] at constant [NH(4)Cl] (10 mM) or increasing [NH(4)Cl] at constant [NH(3)] (0.045 mM) with pH varying in both cases. At -70 mV, the NH(4)Cl-induced current was barely detectable at pH 6.5, 0.01 mM NH(3), but increased successively at pH 7.5, 0.1 mM NH(3) and pH 8.5, 1 mM NH(3). In contrast, NH(4)Cl-associated currents were independent of changes of the [NH(4)Cl] at constant [NH(3)] and variable pH. Similar results with respect to acidification, depolarization and inward current in response to concentration and pH changes were obtained with trimethylamine HCl. Increasing concentrations of the weak acid propionate led to a reduction of the NH(4)Cl-induced current. These data suggest that NH(3) entry may induce local alkalinization that, in turn, may trigger the opening of a conductance for NH(4)(+) or trimethylamine-H(+) entry.