The ability of the kidney to reabsorb bicarbonate is held to be a function of plasma CO(2) tension, carbonic anhydrase activity, and potassium stores. The effects of alterations of extracellular volume on bicarbonate reabsorption were studied in dogs whose arterial Pco(2) was kept constant at 40 mm Hg (range 35-45 mm Hg). The effect of extracellular volume expansion was studied in dogs receiving hypertonic bicarbonate and isotonic saline, isotonic saline alone (two of the animals in this group received HCl to lower the plasma bicarbonate concentration), and isotonic bicarbonate. The results were similar in each group. Extracellular volume expansion depressed bicarbonate reabsorption. This depression was related not to changes in glomerular filtration rate (GFR) or bicarbonate concentration, but to the increase of fractional sodium excretion. In addition, volume expansion with bicarbonate increased chloride excretion. Bicarbonate loading was performed in two groups of dogs in which effective expansion of extracellular volume was minimized by hemorrhage or acute constriction of the thoracic vena cava. Both groups demonstrated enhanced bicarbonate reabsorption relative to that seen in the volume-expanded groups. Release of the caval ligature promptly decreased bicarbonate reabsorption. Plasma potassium decreased in all animals studied, but the changes in bicarbonate reabsorption noted could not be related to the decrease. This study demonstrates that the state of effective extracellular volume is a major determinant of bicarbonate reabsorption by the kidney.