Anaerobic habitats often have low pH and high concentrations of fermentation acids, and these conditions can inhibit the growth of many bacteria. The toxicity of fermentation acids at low pH was traditionally explained by an uncoupling mechanism. Undissociated fermentation acids can pass across the cell membrane and dissociate in the more alkaline interior, but there is little evidence that they can act in a cyclic manner to dissipate protonmotive force. Fermentation acid dissociation in the more alkaline interior causes an accumulation of the anionic species, and this accumulation is dependent on the pH gradient (delta pH) across the membrane. Fermentation acid-resistant bacteria have low delta pH and are able to generate ATP and grow with a low intracellular pH. Escherichia coli O157:H7 is able to decrease its intracellular pH to 6.1 before growth ceases, but this modest decrease in delta pH can only partially counteract the toxic effect of fermentation anion accumulation. Fermentation acid-resistant bacteria are in most cases Gram-positive bacteria with a high intracellular potassium concentration, and even acid-sensitive bacteria like E. coli K-12 have increased potassium levels when fermentation acids are present. Intracellular potassium provides a counteraction for fermentation acid anions, and allows bacteria to tolerate even greater amounts of fermentation anions. The delta pH-mediated anion accumulation provides a mechanistic explanation for the effect of fermentation acids on microbial ecology and metabolism.