Increased hydrogen (H-2) levels are known to inhibit H-2 formation in Caldicellulosiruptor saccharolyticus. To investigate this organism's strategy for dealing with elevated H-2 levels the effect of the hydrogen partial pressure (P-H2) on fermentation performance was studied by growing cultures under high and low P-H2 in a glucose limited chemostat setup. Transcriptome analysis revealed the upregulation of genes involved in the disposal of reducing equivalents under high P-H2 like lactate dehydrogenase and alcohol dehydrogenase as well as the NADH-dependent and ferredoxin-dependent hydrogenases. These findings are in line with the observed shift in fermentation profiles from acetate production to the production of acetate, lactate and ethanol under high P-H2. Moreover, differential transcription was observed for genes involved in carbon metabolism, fatty acid biosynthesis and several transport systems. In addition, presented transcription data provide evidence for the involvement of the redox sensing Rex protein in gene regulation under high P-H2 cultivation conditions. Copyright (C) 2012, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.