Abstract: Acid Tolerance Response (ATR) in Shigella sonnei and Shigella flexneri was induced by pre-exposing the mid exponential phase cultures at sub lethal pH of 4.5 for 90 min before challenging them in lethal pH of 3.0. The ATR was exhibited by both species with S. flexneri displaying a higher tolerance to lethal acid killing. Analyses of protein profiles of both unadapted and adapted cells using 2-dimensional gel electrophoresis (2D-PAGE) revealed that the acid adapted cells of S. sonnei demonstrated differential expression of 19 Acid Stress Proteins (ASPs). Five of these proteins were synthesized de novo, 11 were upregulated while three other proteins were repressed. In S. flexneri, two proteins were synthesized de novo, four upregulated and two proteins were repressed. Two of these proteins with estimated molecular weights of 14.1 and 15.1 kDa and isoelectric points (pI) of 5.50 and 5.58, respectively were found to be consistently induced in both species. An inducible ATR in Shigella may protect the bacteria from environmental pH stress and aid in their pathogenesis. The detection of proteins important for ATR may present novel targets for antimicrobial intervention.