Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We use a database for acute aquatic toxicity, and focus on some well-defined chemical classes. Potency is strongly related to hydrophobicity and vulnerability differences between species are small for narcotic compounds. Potencies show less relation with hydrophobicity and interspecies differences are larger for organophosphate- and carbamate insecticides. Photosynthesis inhibitors generally act narcotic to animals, but were more potent for algae. Using these potencies and vulnerabilities, acute toxicity values were well predicted by the proposed approach (within a factor of 3-6). The proposed approach has potential for predicting toxicity for untested species-compound combinations; however, there is a need for a better definition of 'mode of action' in ecotoxicology. © 2007 Elsevier Inc. All rights reserved.