Spirotetramat is a potent insecticide against plant sapping insects applied worldwide. Once activated in the plant, it targets the first enzyme of the lipid biosynthetic pathway acetyl-CoA decarboxylase. Its impact on target insect survival and fecundity has been studied extensively. Detailed phenotypic analyses of spirotetramat exposure, however, have not been reported, but are important parameters for an integral risk assessment. An yet unaddressed hypothesis is that spirotera-mat affects the efficiency of the lipid-based eggshell and cuticle barriers against xenobiotic penetration and water loss. To analyse the effects of spirotetramat on surface lipids, Drosophila melanogaster flies are fed with spirotetramat. These flies are viable but sensitive to drought compared to non-treated flies. Eggs from spirotetramat-fed females desiccate and take up xenobiotics at lower temperatures than control eggs; no larvae hatch of these eggs. Larvae fed with spirotetramat are sensitive to xenobiotics uptake and do not moult to the next stage. Interestingly, in adult spirotetramat-treated flies, the leg joints and tarsae become more sensitive to xenobiotics penetration than in control flies, whereas the remaining body retains its integrity. Loss of inward barrier efficiency in these flies may also explain their enhanced sensitivity to contact insecti-cides such as DDT. Overall, our data indicate that spirotetramat modulates the bidirectional surface barrier efficiency in D. melanogaster at all stages. This fitness reduction is, as opposed to immediate effects on survival and fecundity, a remote consequence of spirotetramat toxicity. This notion should be taken into consideration during risk assessment of spirotetra-mat toxicity also on non-target insects.