To investigate the influence of prolonged acid exposure on the gene expression, transcripts of Helicobacter pylori, grown under pH 5.5 and pH 7.4 for five successive passages, were analysed by differential display PCR. Eight genes were regulated by prolonged acid exposure. These genes included topA, tufB, ureB, flaA, atoE in the H. pylori genome and a cDNA fragment with 54% identity of the predicted amino acid sequence to a Bacillus cereus YkoW protein. The remaining two cDNA fragments had no significant homology to known sequences. Our data suggest that most of these genes might be required for the resistance of H. pylori to prolonged acid exposure.