AbstractSalmonella typhimuriumperiodically confronts acid environments during its life. These situations arise in chemically compromised ponds, soil, degradative cellular organelles, host digestive systems, and may even result from byproducts of their own metabolism. The levels of acid that are encountered range from mild to extreme. As a neutralophile,S. typhimuriumprefers to grow in pH environments above pH 5.5. They can survive down to pH 4 for extended periods of time. However, the limits of endurance can be stretched if the organisms are first adapted to a moderate acid pH before exposing them to acidity below pH 4.0. This adaptation, called the acid-tolerance response (ATR), includes several log phase and stationary phase systems. Some of these systems are dependent on an alternate sigma factor for RNA polymerase called O−s, whereas other systems are O−s-independent. A key to the ATR is the synthesis of a series of acid shock inducible proteins (ASPs), 51 for log phase ATR and 15 for stationary phase ATR. Some of these ASPs require O−sfor their syndiesis; others require the participation of the ferric uptake regulator protein Fur. Effective acid tolerance involves RecA-independent DNA repair systems, iron, and facets of fatty acid metabolism. Aspects of medium composition and carbon metabolism are also known to influence the nature of acid tolerance in this organism. In addition to aiding survival in the natural non-host environment, aspects of acid tolerance are also tied to virulence, as evidenced by the involvement of the mouse virulence locusmviAand the fact that acid-sensitive strains ofS. typhimuriumexhibit reduced virulence. This review summarizes these aspects of acid adaptation and includes a discussion of acid-regulated gene expression.