A large part of the xenobiotics that are encountered as aquatic pollutants can be regarded as belonging to the so-called class 1 or baseline toxicity compounds. It is generally accepted that these compounds act through or can be considered to act through one and the same mechanism. A second important class of aquatic pollutants is formed by the slightly more toxic class 2 or polar narcosis compounds; this class of compounds is made up of, among others, phenols, anilines and similar slightly polar species and can also be considered to act through a single toxic mechanism. It has been shown that for both groups of chemicals the acute aquatic toxicity can be adequately modelled using a single-parameter quantitative structure-activity relationship (QSAR) equation based on log Kow. Furthermore, it has been shown that for compounds with a log Kow above about 2·7 the distinction between the two classes, and hence between the two associated QSARs, breaks down. Apparently, the more specific mode of action, if there indeed is such a separate mechanism, converges to baseline toxicity at high log Kow. It therefore remains to be demonstrated whether this so-called ‘polar narcosis’ really is a distinct mode of action or just a perturbation of the baseline toxicity mechanism due to the more polar nature of the compounds. The chemical domain of class 1 and class 2 type compounds has been defined as a set of (sub)structural rules or structural alerts. In the current paper we constructed a PLS discriminant analysis QSAR model, based on non-empirical molecular descriptors, that is able to distinguish between class 1 and class 2 compounds. We also constructed a PLS regression analysis QSAR model, based upon the same set of molecular descriptors, that is capable of predicting the acute aquatic toxicity to fish for a combined set of class 1 and class 2 chemicals. Interestingly, the prime descriptor for both discrimination of class 1 and class 2 compounds and bringing them together in the toxicity prediction model is Q−, which is a measure of the hydrogen bond acceptor capacity of a molecule.