Stewart's quantitative physical chemical approach enables us to understand the acid-base properties of intravenous fluids. In Stewart's analysis, the three independent acid-base variables are partial CO2 tension, the total concentration of nonvolatile weak acid (ATOT), and the strong ion difference (SID). Raising and lowering ATOT while holding SID constant cause metabolic acidosis and alkalosis, respectively. Lowering and raising plasma SID while clamping ATOT cause metabolic acidosis and alkalosis, respectively. Fluid infusion causes acid-base effects by forcing extracellular SID and ATOT toward the SID and ATOT of the administered fluid. Thus, fluids with vastly differing pH can have the same acid-base effects. The stimulus is strongest when large volumes are administered, as in correction of hypovolaemia, acute normovolaemic haemodilution, and cardiopulmonary bypass. Zero SID crystalloids such as saline cause a 'dilutional' acidosis by lowering extracellular SID enough to overwhelm the metabolic alkalosis of ATOT dilution. A balanced crystalloid must reduce extracellular SID at a rate that precisely counteracts the ATOT dilutional alkalosis. Experimentally, the crystalloid SID required is 24 mEq/l. When organic anions such as L-lactate are added to fluids they can be regarded as weak ions that do not contribute to fluid SID, provided they are metabolized on infusion. With colloids the presence of ATOT is an additional consideration. Albumin and gelatin preparations contain ATOT, whereas starch preparations do not. Hextend is a hetastarch preparation balanced with L-lactate. It reduces or eliminates infusion related metabolic acidosis, may improve gastric mucosal blood flow, and increases survival in experimental endotoxaemia. Stored whole blood has a very high effective SID because of the added preservative. Large volume transfusion thus causes metabolic alkalosis after metabolism of contained citrate, a tendency that is reduced but not eliminated with packed red cells. Thus, Stewart's approach not only explains fluid induced acid-base phenomena but also provides a framework for the design of fluids for specific acid-base effects.