The challenge of maintaining a cytoplasmic pH that is much lower than the external pH is central to the adaptation of extremely alkaliphilic Bacillus species to growth at pH values above 10. The success with which this challenge is met may set the upper limit of pH for growth in these bacteria, all of which also exhibit a low content of basic amino acids in proteins or protein segments that are exposed to the outside bulk phase liquid. The requirement for an active Na(+)-dependent cycle and possible roles of acidic cell wall components in alkaliphile pH homeostasis are reviewed. The gene loci that encode Na+/H+ antiporters that function in the active cycle are described and compared with the less Na(+)-specific homologues thus far found in non-alkaliphilic Gram-positive prokaryotes. Alkaliphilic Bacillus species carry out oxidative phosphorylation using an exclusively H(+)-coupled ATPase (synthase). Nonetheless, ATP synthesis is more rapid and reaches a higher phosphorylation potential at highly alkaline pH than at near-neutral pH even though the bulk electrochemical proton gradient across the coupling membrane is lower at highly alkaline pH. It is possible that some of the protons extruded by the respiratory chain are conveyed to the ATP synthase without first equilibrating with the external bulk phase. Mechanisms that might apply to oxidative phosphorylation in this type of extensively studied alkaliphile are reviewed, and note is made of the possibility of different kinds of solutions to the problem that may be found in new alkaliphilic bacteria that are yet to be isolated or characterized.