Blood acid­base and ionic balance in freshwater bivalves is affected by the relative activities of epithelial Na+ and Cl- transporters. In the unionid Carunculina texasensis, the Na+/H+ exchanger is the predominant epithelial transporter that affects acid­base state, while Cl-/HCO3- exchange is of lesser importance. In the corbiculid Corbicula fluminea, Cl- and Na+ transport are both significant components affecting acid­base state. Serotonin (5-hydroxytryptamine, 5-HT) stimulates Na+ and Cl- transport in both species. In C. texasensis, the effect of exogenous serotonin is four times greater on Na+/H+ exchange than on Cl-/HCO3- transport, resulting in an increase in acid secretion and a rise in blood pH. In a Na+-free environment, serotonin had no effect on blood acid­base state in C. texasensis. In C. fluminea, the acid­base consequences of serotonin stimulation of Na+/H+ exchange were offset by similar increases in Cl-/HCO3- exchange and by alterations in blood PCO(sum) in medium containing Na+. In Na+-free medium, stimulation of the Cl- transporter with 5-HT resulted in a decrease in blood pH. The differences between these two species are related to the reliance of C. fluminea on Cl- as the major anion in the blood, requiring high levels of epithelial Cl- transport. In C. texasensis, the anionic component of the blood consists of both Cl- and HCO3- and these ions are interchangeable over a wide concentration range. Extracellular acid­base balance in freshwater bivalves is governed, in part, by epithelial ion transporters.