Biotic ligand models (BLM) explicitly accounting for hypothetical interactions with biotic ligands and bioavailability as dictated by water chemistry have been developed for various metals and different organisms. It is only recently that BLMs for plants have received increasing attention. Lettuce is one of the most important vegetable crops in the world. This study investigated the impacts of Ca(2+), Mg(2+), K(+), Na(+) and pH, on acute toxicity of Ni and Cd to butter-head lettuce seedlings (Lactuca sativa L.). 4-day assays with the root elongation inhibition (REI) as the endpoint were performed in hydroponic solutions. Magnesium was found to be the sole cation significantly enhancing the median inhibition concentration (IC50) of Ni(2+) with increasing concentration. By incorporating the competitive effects of Mg(2+), the Ni-toxicity prediction was improved significantly as compared to the total metal model (TMM) and the free ion activity model (FIAM). The conditional stability constants derived from the Ni-BLM were log K MgBL = 2.86, log K NiBL = 5.1, and f NiBL (50%) = 0.57. A slight downtrend was observed in the 4-d IC50 of Cd(2+) at increasing H(+) concentrations, but this tendency was not consistent and statistically significant (p = 0.07) over the whole range. The overall variations of Cd-toxicity within the tested Na(+), K(+), Ca(2+) and Mg(2+) concentration ranges were relatively small and not statistically significant. 80 % of lettuce REI by Cd could be explained using both TMM and FIAM instead of BLM in the present study. Thus, the mechanistically underpinned models for soil quality guidelines should be developed on a metal-specific basis across different exposure conditions.