Ultrafiltration processes normally operate with constant transmembrane pressure. The tradition of such control derives from its inherent simplicity. Both fundamental and practical considerations suggest, however, that ultrafiltration processes should be controlled by maintaining a constant wall concentration (C-w) of fully retained solutes. Since protein sieving, solubility, and adsorption losses as well as time and area optimization are dependent on C-w, we investigated a control strategy using constant C-w instead of constant transmembrane pressure. We explored three different strategies for such control and evaluated the theoretical and industrial implications for single solute systems. The effects of solute wall concentration on process time and product yield were also evaluated. Implementation of this technology required the development of a novel methodology for determination of mass transfer coefficients. The use of C-w technology also led to the development of new optimization schemes for both concentration and diafiltration. Industrial scale processes using constant C-w control have been successfully implemented on several recombinant DNA derived human protein pharmaceuticals. Constant C-w control has eliminated variability in process time, enhanced product yields, and provided insurance of tight protein product quality specifications. Optimum process design based on fundamental filtration theory has replaced empirical development procedures.