In evaluating the effects of toxicants on aquatic communities, consideration should be given to the possibility that several chemicals may be present simultaneously and that joint toxicity is the reason for adverse impacts of pollutants on aquatic environments. Experiments were designed to assess the application of current methodology, classification schemes, and models to explore basic principles used in defining the joint toxicity of chemical mixtures to aquatic organisms. A procedure to identify combined effects of toxicants from the known or predicted toxicity of individual compounds is discussed. The specific end-point used was the 96-h LC50 for juvenile fathead minnows (Pimephales promelas) exposed to individual chemicals, and binary and multiple equitoxic mixtures. The isobole diagram as generated for binary mixtures was successfully used to depict various types of responses and to define chemicals that apparently have similar or different primary modes of toxic action as determined by a whole-organism response. It was confirmed that chemicals with a primary and common mode of toxic action can be modeled by a quantitative structure-activity relationship (QSAR), and that each mode of toxic action should be characterized by a different empirically derived QSAR. Chemicals within several specific QSARs have been determined to be strictly additive in their joint toxicity. Chemicals from different QSARs generally display a less-than-strictly additive joint toxicity. The majority of industrial organic chemicals display a nonspecific or baseline toxicity and are strictly additive in their joint acute toxicity. Less-than-no addition (antagonism), more-than-strictly additive addition (potentiation), or noninteractive joint toxicity are not common biological responses for aquatic organisms exposed to industrial organic mixtures. A concentration additive to slightly less than strictly additive response has been demonstrated for most multiple chemical mixtures during acute tests with aquatic organisms.