ABSTRACT: This study focus a comparative toxicogenomic analysis of the effects of four herbicides (alachlor, ALA, S-metolachlor, S-MET, diuron, DIU, and MCPA-methyl ester, MCPA-ME), one insecticide (carbofuran, CAB), and one fungicide (pyrimethanil, PYR), in the model yeast Saccharomyces cerevisiae, to predict potential cytotoxic effects of these xenobiotics while providing mechanistic clues possibly relevant for experimentally less accessible non-target eukaryotes. The six model pesticides selected have been used worldwide in agricultural activities, at the present time or in the past, and have different modes of action on their target-organisms. Moreover, some of them are currently in Annex 1 of EC Directive 1107/2009 (repealing 91/414), that is they are in use in the EU, but having some ecotoxicological concerns (e.g. S-MET, PYR, MCPA-ME), others have their use restricted and/or are priority substances under the Water Framework Directive (e.g. ALA, DIU), and one was banned (e.g. CAB). We used genome microarrays to obtain gene expression profiles in S. cerevisiae strain BY4741 upon 2 hours exposure to pesticide concentrations exerting a moderate inhibition of yeast growth rate. To obtain comparable gene expression profiles representing yeast response to the six different pesticides, all exposure treatments were performed with equitoxic pesticide concentrations that generated equivalent responses at the phenotypic level (namely, 20% growth-inhibitory concentrations, hereafter designated as the pesticide IC20).