In this study, amiodarone, at very low concentrations, produced a clear efflux of K(+). Increasing concentrations also produced an influx of protons, resulting in an increase of the external pH and a decrease of the internal pH. The K(+) efflux resulted in an increased plasma membrane potential difference, responsible for the entrance of Ca(2+) and H(+), the efflux of anions and the subsequent changes resulting from the increased cytoplasmic Ca(2+) concentration, as well as the decreased internal pH. The Deltatok1 and Deltanha1 mutations resulted in a smaller effect of amiodarone, and Deltatrk1 and Deltatrk2 showed a higher increase of the plasma membrane potential. Higher concentrations of amiodarone also produced full inhibition of respiration, insensitive to uncouplers and a partial inhibition of fermentation. This phenomenon appears to be common to a large series of cationic molecules that can produce the efflux of K(+), through the reduction of the negative surface charge of the cell membrane, and the concentration of this cation directly available to the monovalent cation carriers, and/or producing a disorganization of the membrane and altering the functioning of the carriers, probably not only in yeast.