In neurones cultured from chick dorsal root ganglia, application of NH4Cl (3-45 mM) produced a transient inward current followed by a sustained current at negative holding potentials. Methylamines, hydrazine and guanidine were not able to mimic the effects of NH4Cl. The transient, but not the steady current, was inactivated during successive applications of NH4Cl. Challenge with acidic solutions (pH 6.0-6.4) or Ca(2+)-free solutions induced similar currents and abolished NH4Cl-induced transients. Exposure to 10 mM NH4Cl transiently increased cytoplasmic free Ca2+, which then fell to a sustained plateau. NH4Cl-induced membrane depolarization and the concomitant elevation in intracellular Ca2+ can play an important role in modulation of neuronal activity.