How yeast cells respond to cell wall stress is relatively well understood, however, how filamentous fungi cope with cell wall damage is largely unexplored. Here, we report the first transcriptome analysis of Aspergillus niger exposed to the antifungal compounds caspofungin, an inhibitor of -1,3 glucan synthesis, and fenpropimorph, which inhibits ergosterol synthesis. The presence of sub-lethal drug concentrations allowed A. niger to adapt to the stress conditions and to continue growth by the establishment of new polarity axes and formation of new germ tubes. By comparing the expression profile between caspofungin-exposed and non-exposed A. niger germlings, we identified a total of 172 responsive genes out of 14,509 open reading frames present on the Affymetrix microarray chips. Among 165 up-regulated genes, mainly genes predicted to function in (i) cell wall assembly and remodeling, (ii) cytoskeletal organization, (iii) signaling and (iv) oxidative stress response were affected. Fenpropimorph modulated expression of 43 genes out of which 41 showed enhanced expression. Here, genes predicted to function in (i) membrane reconstruction, (ii) lipid signaling, (iii) cell wall remodeling and (iv) oxidative stress response were identified. Northern analyses of selected genes were used to confirm the microarray analyses. The results further show that expression of the agsA gene encoding an -1,3-glucan synthase is up-regulated by both compounds. Using two PagsA-GFP reporter strains of A. niger and subjecting them to 16 different antifungal compounds, including caspofungin and fenpropimorph, we could show that agsA is specifically activated by compounds interfering directly or indirectly with cell wall biosynthesis.