The Schizosaccharomyces pombe plasma membrane Na(+)/H(+) antiporter, SpSod2p, has been shown to belong to the subfamily of yeast Na(+)/H(+) antiporters that only recognize Na(+) and Li(+) as substrates. Nevertheless, most of the studied plasma membrane alkali metal cation/H(+) antiporters from other yeasts have broader substrate specificities, exporting K(+) and Rb(+) as well. Such antiporters probably play two roles in the physiology of cells: the elimination of surplus toxic cations, and the regulation of stable intracellular K(+) content, pH and cell volume. The systematic sequencing of the Sch. pombe genome revealed the presence of an as-yet uncharacterized homolog of the Spsod2 gene (designated Spsod22). Spsod22 and Spsod2 were expressed in Saccharomyces cerevisiae cells lacking their own alkali metal cation efflux systems, and the transport properties of both Sch. pombe antiporters were compared to those of the Sac. cerevisiae Nha1 antiporter expressed under the same conditions. Here we show that SpSod22p has broad substrate specificity upon heterologous expression in Sac. cerevisiae cells and contributes to cell tolerance to high external levels of K(+). Thus, the Sch. pombe genome encodes two plasma membrane alkali metal cation/H(+) antiporters that play different roles in the physiology of the yeast.