The removal of specific antibody in experimental animals has been reported to result in a subsequent increase in antibody to levels equal to (rebound) or exceeding those existing prior to removal (overshoot). Anecdotal reports suggest that rebound antibody synthesis after plasmapheresis may occur in humans with autoimmune disorders. We measured the antibody response to 12 pneumococcal polysaccharide antigens in patients with myasthenia gravis (MG) receiving a variety of therapies in order to determine whether the T-cell-independent IgG response to these antigens was augmented by plasmapheresis. MG patients receiving no immunotherapy or receiving prednisone had pre- and post-immunization titers similar to those of control patients. MG patients receiving prednisone and chronic plasmapheresis had higher pre-immunization titers than did other patient groups and had significantly higher post-immunization titers against multiple pneumococcal serogroups. Aggregate post-immunization geometric mean titers were more than three-fold higher in the plasmapheresis group as compared with other MG treatment groups. Enhancement of antibody response by plasmapheresis was abolished by the concomitant administration of azathioprine. Antibody rebound and overshoot after antibody removal may have important implications for the therapy of immune disorders by plasmapheresis.