In this study, the effects of modifying Ca (0.2-4 mM), Mg (0.05-3 mM), Na (0.75-5 mM), and pH (5.5-7.5) on the chronic toxicity of zinc to juvenile rainbow trout (Oncorhynchus mykiss) were investigated using standard 30-d assays in which survival and growth were monitored. Survival was observed to be a more sensitive end point than growth, and mortality mainly occurred during the initial stages of the exposure. This suggested that the mode of action of zinc toxicity was mainly of an acute nature. A review and analysis of existing literature demonstrated similar results for most other fish species investigated. Overall, up to a 30-fold variation of zinc toxicity was observed, as indicated by no observed effect concentrations varying between 32.7 and 974 microg of Zn L(-1). Increased concentrations of Ca2+, Mg2+, Na+, and H+ (within the tested ranges) resulted in a reduction of chronic zinc toxicity by a factor of 12, 3, >2, and 2, respectively. This suggests the major importance of Ca competing with zinc and protecting against zinc toxicity, which seems to be a ubiquitous concept in fish species (and probably also invertebrate). On the basis of the toxicity data obtained, a chronic biotic ligand model (BLM) was developed that takes into account both chemical speciation of zinc and competition between zinc and the above-mentioned cations. The developed model was able to predict chronic effect concentrations with an error of less than a factor of 2 in most cases. Hence, it was concluded that the chronic Zn BLM can reduce toxicity variability due to bioavailability to a considerable extent and that the BLM can become an important tool in criteria setting and risk assessment practice of zinc and zinc substances.