Systems and methods for performing a red blood cell exchange procedure are disclosed. In one aspect, the flow rates of a replacement fluid (e.g., red blood cells from a healthy donor) and plasma being flowed to a blood source are calculated based on certain parameters of the procedure that are known, including the flow rate of blood being drawn from the source and the volume of replacement fluid to be used during the procedure. The replacement fluid flow rate and the plasma flow rate are calculated in a way that allows for simultaneous depletion of the supply of replacement fluid and achievement of another prescribed process parameter. The other prescribed process parameter depends on the nature of the procedure, namely whether the fluid volume and hematocrit of the source are to change by the end of the procedure or remain the same.
