The influence of salinity on Ag toxicity was investigated in Atlantic killifish (Fundulus heteroclitus) early life-stages. Embryo mortality was significantly reduced as salinity increased and Ag+ was converted to AgCl(solid). However, as salinity continued to rise (>5 ‰), toxicity increased to a level at least as high as observed for Ag+ in deionized water. Rather than correlating with Ag+, Fundulus embryo toxicity was better explained (R2 = 0.96) by total dissolved Ag (Ag+, AgCl2 −, AgCl3 2−, AgCl4 3−). Complementary experiments were conducted with medaka (Oryzias latipes) embryos to determine if this pattern was consistent among evolutionarily divergent euryhaline species. Contrary to Fundulus data, medaka toxicity data were best explained by Ag+ concentrations (R2 = 0.94), suggesting that differing ionoregulatory physiology may drive observed differences. Fundulus larvae were also tested, and toxicity did increase at higher salinities, but did not track predicted silver speciation. Alternatively, toxicity began to increase only at salinities above the isosmotic point, suggesting that shifts in osmoregulatory strategy at higher salinities might be an important factor. Na+ dysregulation was confirmed as the mechanism of toxicity in Ag-exposed Fundulus larvae at both low and high salinities. While Ag uptake was highest at low salinities for both Fundulus embryos and larvae, uptake was not predictive of toxicity.