Phenolic compounds exist in abundance in the environment as the product of natural and synthetic processes and can be harmful, stress-inducing exotoxins. Bisphenol-A (BPA), butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) are phenol-based compounds found in polycarbonate plastics and food preservatives and therefore have a particularly high degree of human exposure. Exposure to these compounds has been associated with numerous diseases, yet their mechanisms of action are not well understood. A quantitative evaluation of growth of wild type and haploid deletion strains was used to identify the genes that modulate response to phenol stress induced by BPA, BHA, and BHT in Saccharomyces cerevisiae. Exposure to phenol stress in wild type yeast induces the unfolded protein response (UPR). The UPR is a conserved cellular process that responds to stressors that cause unfolded proteins to accumulate in the endoplasmic reticulum, eventually inducing cell death. In yeast, one portion of the UPR is activated when unfolded proteins bind to inositol-requiring enzyme 1 protein (Ire1p). Ire1p then oligomerizes, activating HAC1 pre-mRNA splicing; Hac1 is a transcription factor that promotes expression of chaperone proteins that refold or degrade unfolded proteins. Ire1-GFP showed clustering after treatment with BHT for 2 hours. Ergosterol is similar to cholesterol in humans and maintains membrane fluidity; mutants with deleted ergosterol genes do not produce ergosterol and were identified in the deletion mutant screen as possible modulators of phenol stress response. This suggests that like the UPR, ergosterol biosynthesis is affected by phenols and reduced membrane fluidity may potentially inhibit Ire1p movement and oligomerization. To test this hypothesis, we treated ergosterol pathway deletion mutants Δerg 2, ∆erg6 and ∆erg24 with BPA, BHA, and BHT during 12 hour time courses. We measured HAC1 pre-mRNA splicing using RT-PCR. Strains deleted for genes encoding proteins in the ergosterol biosynthesis pathway had growth rates that were below wild type growth rates when exposed to BPA, BHA, and BHT and showed lower levels of UPR induction after phenol stress. These data demonstrate an important pathway through which common phenols act in yeast, which may inform research on human exposure to these chemicals.