Effects of ion-ion interactions on metal toxicity to lettuce Lactuca sativa were studied based on the electrical potential at the plasma membrane surface (ψ0 ). Surface interactions at the proximate outside of the membrane influenced ion activities at the plasma membrane surface ({M(n+)}0). At a given free Cu(2+) activity in the bulk medium ({Cu(2+)}b), additions of Na(+), K(+), Ca(2+), and Mg(2+) resulted in substantial decreases in {Cu(2+)}0. Additions of Zn(2+) led to declines in {Cu(2+)}0, but Cu(2+) and Ag(+) at the exposure levels tested had negligible effects on the plasma membrane surface activity of each other. Metal toxicity was expressed by the {M(n+)}0 -based strength coefficient, indicating a decrease of toxicity in the order: Ag(+) > Cu(2+) > Zn(2+). Adsorbed Na(+), K(+), Ca(2+), and Mg(2+) had significant and dose-dependent effects on Cu(2+) toxicity in terms of osmolarity. Internal interactions between Cu(2+) and Zn(2+) and between Cu(2+) and Ag(+) were modeled by expanding the strength coefficients in concentration addition and response multiplication models. These extended models consistently indicated that Zn(2+) significantly alleviated Cu(2+) toxicity. According to the extended concentration addition model, Ag(+) significantly enhanced Cu(2+) toxicity whereas Cu(2+) reduced Ag(+) toxicity. By contrast, the response multiplication model predicted insignificant effects of adsorbed Cu(2+) and Ag(+) on the toxicity of each other. These interactions were interpreted using ψ0, demonstrating its influence on metal toxicity.