['To determine the relationship between the strong ion difference (SID) of a diluting crystalloid and its metabolic acid-base effects on in vitro blood dilution.', 'Prospective in vitro study.', 'University research laboratory.', 'Normal human blood.', "Three solutions were prepared, each with [Na] 140 mmol/L. [Cl-] for solutions 1, 2, and 3 was 120, 110, and 100 mmol/L, respectively, the other anion being HCO3-. SID values were thus 20, 30, and 40 mEq/L, respectively. Serial dilutions of well-oxygenated fresh venous blood were performed anaerobically by using each of solutions 1-3 as well as 0.9% saline (SID = 0 mEq/L) and Hartmann's solution (SID = -4 mEq/L).", 'Blood gas and electrolyte analyses were performed before and after each dilution. Apart from dilutions with solution 3 (crystalloid SID 40 mEq/L) during which plasma SID did not change, plasma SID decreased during hemodilution. In contrast, base excess increased during hemodilution with solutions 3 and 2 (crystalloid SID 40 mEq/L and 30 mEq/L, respectively) and decreased only with the remaining three solutions. The relationships between hemoglobin concentrations and both plasma SID and whole blood base excess throughout dilution were linear, with slopes proportional to the SID of the diluent in each case. Linear regression revealed that the SID of crystalloid producing a zero base excess/hemoglobin concentration slope during blood dilution (i.e., no change in metabolic acid-base status) is 23.7 mEq/L.'] Does crystalloid strong ion difference determine metabolic acid-base change during in vitro hemodilution?