Zebrafish larvae ( Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca 2+ uptake, copper and nickel also decreased Ca 2+ uptake, suggesting that the epithelial transport of all these metals is through Ca 2+ pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca 2+ levels, indicating that the reduction of Ca 2+ uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na +, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K + were also observed, although they were not as pronounced or frequent as Na + losses. None of the metals tested inhibited Na + uptake in zebrafish (Na + uptake was in fact increased with exposure) and the observed losses of Na +, K +, Ca 2+ and Mg 2+ were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na +).