Changes of calcium currents with intracellular pH (pHi) were investigated in chick dorsal root ganglion (DRG) neurones. High-threshold calcium currents decreased after extracellular application of a permeable weak acid, sodium acetate (CH3COONa), and increased when applying a permeable weak base, ammonium chloride (NH4Cl), whereas both compounds were ineffective against the low-threshold calcium current. These weak electrolytes, employed to change pHi, did not alter the kinetic and steady-state parameters of activation and inactivation of the calcium current. Extracellular application of concanavalin A (Con A) and wheat germ agglutinin to elevate pHi increased the high-threshold calcium current. Their effect developed within 2-5 min and was independent of lectin concentration varied from 0.1 to 1 mg/ml. The lectin effects were greatly diminished if Na/H exchange was blocked by amiloride or suppressed by low external sodium. Succinilated Con A and Con A in the presence of D-mannose were less effective. Calcium currents were recorded simultaneously with the pHi, monitored with a proton-sensitive microelectrode. It was found that 50% inhibition of the calcium current occurred at pHi of 6.5. Histidine-specific reagents--diethylpyrocarbonate, Rose Bengal and Methylene Blue--prevented the modulation of the calcium conductance by CH3COONa and NH4Cl. Extracellular baclofen and theophylline or intracellular phorbol esters, staurosporine, calmodulin antagonists R24571 and W-13, and neomycine failed to prevent the modulation of the calcium current by weak electrolytes. These observations are consistent with an interaction between intracellular protons and calcium channels.