The biosynthesis of (toxic) fungal secondary metabolites has been suggested to constitute an important resistance mechanism against antagonistic animals. By using an insect-fungus competition model system (Aspergillus nidulans and Drosophila melanogaster larvae), we found further support for a significant role of global secondary metabolite regulation (via blocking the formation of the velvet complex, Δ veA) in resistance against competing insects, yet precocious transcriptional activation of mycotoxin production (by using mutants deleted in a histone deacetylase, Δ hdaA) did not lead to higher insect mortality rates. Blocking specific steps along the sterigmatocystin pathway did not favor insect survival; in contrast, transgenic fungi were more harmful to the fly larvae, suggesting the activation of other resistance mechanisms. Finally, experiments with various strains manipulated in the expression of genes involved in the formation of oxylipins (ppos) suggest an important role of these info-chemicals in driving fungal resistance against competing insects, directly or indirectly related to mycotoxin synthesis. © 2011 Elsevier Ltd and The British Mycological Society.