Therapeutic plasmapheresis has important clinical applications in the treatment of a variety of immunologic and metabolic disorders, with particular benefits in the treatment of autoimmune diseases like rheumatoid arthritis. Widespread use of the current therapy, which involves removal and subsequent replacement of the patient's plasma, is limited by the large cost and potential complications associated with the use of exogenous replacement fluids, e.g. pooled plasma, that are returned to the patient. Selective protein filtration can provide an inexpensive means for separating the immunoglobulin fraction of plasma, which generally contains the pathogenic species, from the albumin fraction, which can then be safely returned to the patient. Although commercial membranes have been developed that appear to have adequate properties for separating albumin and IgG, previous attempts at this selective protein separation have generally been unsuccessful. This failure has been attributed to a number of different phenomena, but the coupling between bulk and membrane transport has made it difficult to determine which of these phenomena actually govern flux and separation efficiency in clinical devices. The objective of our work is to identify the mechanisms that determine filtrate flux and protein separation efficiency using a coordinated experimental and theoretical program. This involves experiments designed to isolate and characterize the important physical phenomena under conditions where data acquisition and subsequent analysis are relatively straightforward. Experiments are also proposed to obtain accurate data for flux and protein separation efficiency in a laboratory scale cross-flow filter using a variety of polymeric membranes with very different physical and chemical properties. The physical insight obtained from these studies will then be applied to the analysis of clinical/industrial devices for the selective filtration of albumin and IgG.