||Physiological effects of carbon dioxide and impact on genome-wide transcript profiles were analysed in chemostat cultures of Saccharomyces cerevisiae. In anaerobic, glucose-limited chemostat cultures grown at atmospheric pressure, cultivation under CO(2)-saturated conditions had only a marginal (<10%) impact on the biomass yield. Conversely, a 25% decrease of the biomass yield was found in aerobic, glucose-limited chemostat cultures aerated with a mixture of 79% CO(2) and 21% O(2). This observation indicated that respiratory metabolism is more sensitive to CO(2) than fermentative metabolism. Consistent with the more pronounced physiological effects of CO(2) in respiratory cultures, the number of CO(2)-responsive transcripts was higher in aerobic cultures than in anaerobic cultures. Many genes involved in mitochondrial functions showed a transcriptional response to elevated CO(2) concentrations. This is consistent with an uncoupling effect of CO(2) and/or intracellular bicarbonate on the mitochondrial inner membrane. Other transcripts that showed a significant transcriptional response to elevated CO(2) included NCE103 (probably encoding carbonic anhydrase), PCK1 (encoding PEP carboxykinase) and members of the IMD gene family (encoding isozymes of inosine monophosphate dehydrogenase).