We used a reactant adsorptive membrane bioreactor separator (or RAMBS) system to examine hydrophobic interaction based binding of human immunoglobillin G (HIgG) on synthetic inicroporous membranes possessing tunable hydrophobicity. Membrane bound FllgG oil being pulsed with papain resulted in Fab being obtained in the flowthrOUgh with Fc remaining bound to the membrane. Oil the other hand, when membrane bound HIgG was pulsed with pepsin, Fc subrragi-nents were obtained in the flowthrough with F(ab')2 remaining bound to the membrane. These product profiles suggest that HIgG bound to the membrane through its middle region. Enzyme linked immunoadsorbent assay (ELISA), sodium dodecyl Sulfate polyacrylamicle gel electrophoresis (SDS-PAGE), and mass spectrometric analysis of eluate samples obtained from the RAMBS experiments provided evidence that the binding of HIgG took place primarily through the segment consisting of the hinge and Cl.12 domain of Fc. The experimental approach described in this papcrcould potentially be more widelyapplicable for studying protein interactions with membrane and surfaces in general.