Studies of bacterial adaptation to alkaline pH have been less extensive to date compared with those of acidic pH. Recent development of novel methods for global analysis of gene expression under various conditions revealed that many genes were induced at high pH. These data led us to question why so many genes are required for adaptation to alkaline pH. The internal pH of bacteria growing at extremely high pH remains unclear because the methods for measuring interior acidic deltapH developed to date are not so accurate, but it is generally accepted that cytoplasmic pH increases with medium alkalization, although the increase is lower than that of the change in medium pH. Therefore, activities of enzymes working in neutral cytoplasm may decrease with cytoplasmic alkalization under extreme alkaline conditions. Based on these findings, we propose in this article that genes whose products have an optimum activity at high pH are induced under alkaline stress to compensate for the decrease in activities of systems functioning at neutral pH.