The E. coli ArsA is involved in arsenic detoxification but the role of yArsA (ArsA homologue of Saccharomyces cerevisiae, encoded by YDL100c ORF) in yeast is still undefined. Disruption of YDL100c ORF is not lethal but the disrupted strain (KO) shows decreased thermotolerance. To study the role of yArsA in thermotolerance, wild type (WT) and KO were grown at 25¢Jand 37¢J, and assayed for the intracellular levels of trehalose accumulation and molecular oxidation, and the biosynthesis of heat shock proteins. The results show that molecular oxidation is higher and trehalose accumulation is lower in KO compared with WT grown at 37¢J, suggesting that increased ROS and decreased trehalose content are the cause of cell death. Further analysis of the expression of ROS defense mechanisms show that there is no significant difference in TSL1 and SOD1 expression in WT and KO grown at 25¢J or 37¢J but the CTT1 expression in KO was much less than WT grown at 37¢J. These observations are consistent with the assays of enzymatic activity of catalase and antioxidant GSH contents. Loss of catalase activity, decreased trehalose contents and Hsp104p expression suggest a deficiency in activation of general but not specific stress response in KO when grown at 37¢J. Therefore, yArsA was involved in signaling the general stress response in stress tolerance network.