The effects of primary, secondary and tertiary methyl- and ethylamines as well as of quaternary ammonium compounds on membrane potential, V _m, and intracellular pH (pH_i) of oocytes from Xenopus laevis were studied using electrophysiological methods. The quaternary ammonium compounds, tetramethyl- (TMA) and tetraethyl- (TEA) ammonium chloride and choline chloride (each 10 mmol/l), affected V _m only slightly. In contrast, primary, secondary and tertiary amines strongly depolarized V _m. Depolarization was inversely proportional to the pK _a of the amines. Trimethylamine (pK _a 9.8) depolarized V _m by 61.7±21.8 mV (n=13) and exerted its half-maximal effect at less than 2 mmol/l. In paired experiments (n=6), trimethylamine (10 mmol/l) reduced V _m only by 5.1±1.3 mV at a bath pH of 6.0, but by 73.2±20.0 mV at pH 7.5, suggesting that the deprotonated, uncharged form of the amines was responsible for the depolarization. pH_i measurements using the Fluka pH-sensitive cocktail 95 293 revealed a short initial alkalinization and a subsequent acidification in the presence of trimethylamine (10 mmol/l). The intracellular acidification proceeded much more slowly than the depolarization. As shown by measurements using a two-electrode voltage-clamp device, the depolarization was associated with an inward current. This trimethylamine-sensitive current, I _m, decreased from-128±82 nA (n=4) at a clamp potential V _c=-70 mV to-3±33 nA at V _c=0 mV. Neither V _m nor I _m were markedly inhibited by GdCl₃, BaCl₂, or amiloride (each 1 mmol/l). Only 1 mmol/l diphenylamine-2-carboxylate (DPC) diminished both responses. The data suggest that the amines modify anion or cation conductances of the oocytes by as yet unknown mechanisms.