In this study, we evaluated the action of two buffer solutions on acid-base equilibrium in cases of hyperchloremic acidosis. Twenty-four patients undergoing major gynecological intraabdominal surgery received 40 mL · kg−1 · h−1 of 0.9% saline per protocol. During surgery, in every patient, hyperchloremic acidosis occurred. At a standard base excess of −7 mmol/L, the patients were randomly assigned to receive within 20 min either a mean of 130 ± 26 mmol of sodium bicarbonate (BIC, 1 M;n = 12) or a mean of 128 ± 18 mmol of tris-hydroxymethyl aminomethane (THAM, 3 M;n = 12). Paco2, pH, serum bicarbonate concentration, standard base excess, and serum concentrations of sodium, potassium, chloride, lactate, phosphate, total protein, and albumin were determined before and 0, 10, and 20 min after buffering. The apparent strong ion difference was calculated as: serum sodium plus serum potassium minus serum chloride minus serum lactate. The effective strong ion difference and the amount of weak plasma acid were calculated by using a computer program. Immediately after buffering, standard base excess increased by 9.8 mmol/L in the BIC group and by 7.2 mmol/L in the THAM group. In both groups, Paco2 and the amount of weak plasma acid remained constant. Mainly because of hypernatremia, the apparent and effective strong ion difference increased in the BIC group by 8.5 and 7.9 mEq/L, respectively. In the THAM group, the apparent strong ion difference remained constant; however, the effective strong ion difference increased by 6.4 mEq/L and the anion gap decreased by 5.8 mmol/L because of the occurrence of an unmeasured cation. In conclusion, in case of buffering with BIC or THAM, the changes in pH were accompanied by, and probably caused by, an increase in strong ion difference.