Competition between microorganisms and arthropods has been shown to be an important ecological interaction determining animal development and spatial distribution patterns in saprophagous communities. In fruit-inhabiting Drosophila, variation in insect developmental success is not only determined by species-specific effects of various noxious filamentous fungi but, as suggested by an earlier study, also by additive genetic variation in the ability to successfully withstand the negative impact of the fungi. If this variation represents a direct adaptive response to the degree to which insect breeding substrates are infested with harmful fungi, genetic variation for successful development in the presence of fungi could be maintained by variation in infestation of resource patches with fungi. We selected for the ability to resist the negative influence of mould by maintaining replicated Drosophila melanogaster populations on substrates infested with Aspergillus nidulans. After five cycles of exposure to the fungus during the larval stage, the selected populations were compared with unselected control populations regarding adult survival and reproduction to reveal an evolved resistance against the fungal competitor. On fungus-infested larval feeding substrates, emerged adults from mould-selected populations had higher survival rates and higher early fecundity than the control populations. In the unselected populations, females had higher mortality rates than males, and a high proportion of both females and males appeared to be unable to lay eggs or fertilise eggs, respectively. When larvae developed on non-infested food we found indications of a loss of resistance to abiotic and starvation stress in the adult stage in flies from the selected populations. This suggests that there are costs associated with an increase in resistance against the microbial competitor. We discuss the underlying mechanisms that might have selected for increased resistance against harmful fungi.