Damp buildings support complex microbial ecosystems that include bacteria, yeasts, molds and mildews. These indoor microbes and their metabolic products have been implicated in causing a group of nonspecific symptoms (fatigue, respiratory distress, eye irritation and so forth) grouped together under labels such as “sick building syndrome” and “damp-building-related illnesses.” The off gassing of industrial solvents, air borne particulates, mycotoxins, volatile organic compounds (VOCs), and combinations thereof all have been implicated as causes of this elusive syndrome. Our laboratory has pioneered the application of genetic model organisms to study the physiological effects of VOCs produced by filamentous fungi isolated from indoor environments. We have focused on several eight-carbon VOCs responsibility for the musty odors found in water-damaged indoor spaces. The toxigenic potential of these fungal VOCs has been explored in Drosophila melanogaster, Arabidopsis thaliana and Saccharomyces cerevisae. We have found that exposure to mixtures of VOCs emitted by numerous species of molds isolated from flooded homes cause toxicity to third instar larvae of D. melanogaster. Further, exposure to chemical standards of 1-octen-3-ol (“mushroom alcohol”) cause neurotoxic symptoms in adult flies that can be dissected at the molecular level using GFP-linked markers, confocal microscopy, and mutant analysis. In flies, a low concentration of 1-octen-3-ol caused Parkinsonian symptoms, reduced dopamine levels and was associated with dopaminergic neuron degeneration, while over-expression of the vesicular monoamine transporter (VMAT) rescued the dopamine toxicity and neurodegeneration. Similarly, 1-octen-3-ol stimulated a NO mediated inflammatory response in nervous and respiratory tissues of D. melanogaster. We confirmed the toxicity of 1-octen-3-ol in human cell culture using both embryonic stem lines and cell lines that express the human plasma membrane dopamine transporter. In other studies using the plant model Arabidopsis thaliana, we showed that 1-octen-3-ol inhibited seed germination and caused bleaching of seedlings. Unexpectedly, we also showed that volatile mixtures emitted from several species of Trichoderma isolated from a flooded homeenhanced plant growth. This growth enhancement was dependent on age of the plant, the species of Trichoderma, the length of exposure, and the concentration of emitted volatiles. However, the underlying molecular mechanisms by which 8-carbon VOCs negatively impact organisms have not yet been elucidated. To this end, we screened the yeast knockout library using a lethal concentration of 1-octen-3-ol and found that 91 genes (out of 4976) were resistant. When the resistant strains were classified using the Saccharomyces Genome Database, the most statistically significant biological processes were endosomal transport (24.2%), protein targeting (20.9%) and proteolysis involved in cellular protein catabolic process (17.6%). We are continuing our screens in yeast at sublethal concentrations of 1-octen-3-ol in order to dissect the molecular mechanisms involved in the physiological processes mediated by this ubiquitous fungal metabolite. In conclusion, volatile-mediated signaling among filamentous fungi is commonand complex. Several common eight carbon fungal VOCs show multiple, concentration-dependent effects on genetic models representing the animal, fungal and plant kingdoms. Mycologists and other biologists who study fungi should recognize that fungal aroma compounds are more than “just smells.” They function to transmit molecular signals that have numerous physiological effects both positive and negative, on each other and other organisms in the same ecosystem. Future studies on “mycobiomes” of built environments no doubt will reveal many interesting new insights into the roles of biogenic VOCs in the microbial ecosystems associated with indoor environments.