The efficacy of plasma exchange in the removal of immunoglobulins (IgG, IgM, IgA), complement components (C1q, C4, C3), alpha 1-antitrypsin, alpha 2-macroglobulin, and transferrin was studied by analysis of pre- and postexchange serum samples and the plasma removed both in a healthy volunteer and in five patients undergoing therapeutic plasma exchange. In the healthy volunteer, the measured reduction in serum concentration and the measured amount removed for each component was compared with values predicted by a physical model. For all components except IgM, the sum of the measured amount removed during the procedure and the calculated amount present in the circulation progressively exceeded the calculated intravascular amount present before plasma exchange. This was particularly the case for C4, C3, alpha 1-antitrypsin, and alpha 2-macroglobulin and may be explained by influx from the extra- to the intravascular compartment during the procedure. Influx also occurred in the patients. We conclude that, except for IgM, the actual amount of a component that has been removed should be assessed for proper evaluation of the efficacy of PE.