The purpose of this study was to examine broad-scale correlation between presence of priority substances and whole effluent toxicity (WET) across a range of industry types. Using regression analysis, we examined how chemical-based inferred toxicity predicted measured WET of the effluents. Whole effluent toxicity was determined using a suite of acute and chronic bioassays; chemical-based toxicity was inferred from concentrations of priority chemicals and from published chemical toxicity values. When inferred toxicity was corrected for bioavailable metal and ion concentrations, 43% of the variability in measured toxicity was explained. For many industries, priority contaminants accounted for WET, and their toxic action was generally additive. However, industry-specific analysis of the residuals highlighted effluent types for which there was over one order of magnitude variation in inferred and measured toxicity. In particular, chemical-based assessments tended to overestimate toxicity of effluents containing high concentrations of metals and to underestimate toxicity of pulp mill effluents.