The biotic ligand model (BLM) was developed to explain and predict the effects of water chemistry on the acute toxicity of metals to aquatic organisms. The biotic ligand is defined as a specific receptor within an organism where metal complexation leads to acute toxicity. The BLM is designed to predict metal interactions at the biotic ligand within the context of aqueous metal speciation and competitive binding of protective cations such as calcium. Toxicity is defined as accumulation of metal at the biotic ligand at or above a critical threshold concentration. This modeling framework provides mechanistic explanations for the observed effects of aqueous ligands, such as natural organic matter, and water hardness on metal toxicity. In this paper, the development of a copper version of the BLM is described. The calibrated model is then used to calculate LC50 (the lethal concentration for 50% of test organisms) and is evaluated by comparison with published toxicity data sets for freshwater fish (fathead minnow, Pimephales promelas) and Daphnia.