In the present study, the individual effects of Ca, Mg, and pH on the chronic toxicity of Ni to Daphnia magna were examined in a series of 21-d reproduction tests in synthetic test solutions. Based on the linear increase of 21-d median effective concentrations expressed as Ni2+ activity (21-d EC50Ni2+) with increasing activities of Ca2+ and Mg2+, the effects of Ca and Mg were modeled according to single-site competition with log KCaBL = 3.53 and log KMgBL = 3.57 (BL = biotic ligand). Because the increase of 21-d EC50Ni2+ with increasing H+ activity was nonlinear, the effect of pH could not be described appropriately by single-site competition between Ni2+ and H+. Instead, the effect of pH was modeled based on an empirical linear relationship between pH and 21-d EC50pNi2+* (equal to -log [21-d EC50Ni2+ corrected for the presence of Ca and Mg]) and was superimposed on the effects of Ca and Mg. For all test solutions used for model development, the developed model predicted the observed 21-d EC50 expressed as dissolved Ni concentration with an error of less than a factor of two. The importance of dissolved organic carbon in protecting D. magna against chronic Ni toxicity was demonstrated by conducting 21-d reproduction tests in a series of Ni-spiked natural waters. Because the model tended to systematically overestimate chronic Ni toxicity in these natural waters, it was further optimized to yield more accurate predictions in natural waters. Although some room still exists for improvement, the developed model is, to our knowledge, the first to present a useful tool for assessing the risk of Ni to aquatic invertebrates.