The understanding of the molecular mechanisms that may contribute to counteract the deleterious effects of organic acids as fungistatic agents is essential to guide suitable preservation strategies. In this work, we show that the recently identified transcription factor Haa1p is required for a more rapid adaptation of a yeast cell population to several weak acids food preservatives. Maximal protection is exerted against the short-chain length acetic or propionic acids. The transcription of nine Haa1p-target genes, many of which predicted to encode membrane proteins of unknown or poorly characterized function, is activated under weak acid stress. The Haa1-regulated genes required for a more rapid yeast adaptation to weak acids include TPO2 and TPO3, encoding two predicted plasma membrane multidrug transporters of the major facilitator superfamily, and YGP1, encoding a poorly characterized cell wall glycoprotein. The acetic acid-induced-prolongation of the lag phase of unadapted cell populations lacking HAA1 or TPO3, compared with wild-type population, was correlated with the level of the acid accumulated into the stressed cells. (c) 2005 Elsevier Inc. All rights reserved.