Oral streptococci produce large quantities of organic acids as the end-products of carbohydrate fermentation. In an approach to determine if oral streptococci exhibit differential sensitivities to organic acid anions, we determined the effects of formate, lactate, and acetate on intracellular pH maintenance, glycolysis, and growth of Streptococcus mutans and Streptococcus sanguis. Growth was determined as maximum culture optical density in the presence of the organic acid anions at pH 7.1, 6.7, 6.3, and 6.1, and the effects of the anions on glycolytic activity and intracellular pH were determined at pH 7.0 and 5.0. At pH 7.1, the organic acid anions had little effect on growth of either species. At the lower pH values, all of the anions reduced the maximum culture optical density of both species in a pH- and concentration-dependent manner, with S. sanguis being more sensitive to growth inhibition than S. mutans. The organic acid anions had little or no effect on glycolytic activity of either species at pH 7.0. However, all of the organic acid anions tested reduced glycolytic activity at pH 5.0 in a concentration-dependent manner, with S. sanguis being more sensitive than S. mutans. The inhibition of glycolysis could be related to the pKa of the organic acid, with formate and lactate being more inhibitory than acetate. The organic acid anions decreased the intracellular pH of S. mutans and S. sanguis, glycolyzing at an extracellular pH of 5.0, such that the reduction in glycolytic activity caused by the organic acid anions could be directly attributed to the fall in intracellular pH. In conclusion, the production of lactic acid in plaque would not only lower pH, thereby having a disadvantageous effect on less aciduric oral streptococci, such as S. sanguis, but would also increase their sensitivity to the effects of low pH, helping S. mutans to become more dominant.