One hundred fourteen pre- and postplasma exchange (PE) serum protein electrophoretograms and serum IgG, IgA, and IgM levels obtained during a 4-month period from 23 patients were evaluated. The interval between PE sessions varied from once daily to approximately once monthly. Typically, post-PE patterns had decreased alpha-1, decreased alpha-2, decreased beta, and decreased gamma fractions. The average percentage decreases of the immunoglobulins subsequent to PE were as follows: IgG, 52%; IgA, 55%; and IgM, 51%. There was a high linear correlation between the pre- and post-PE concentrations of IgG and IgA, whereas correlation of pre- and post-PE IgM concentrations was much lower. All IgG, IgA, and IgM levels (100%) returned to their respective reference intervals before subsequent PE when procedures were scheduled at least 2 weeks apart. When procedures occurred 1 week apart or less, only 1 IgG level (1%) returned to its reference interval, whereas 68 IgA (73%) and 74 IgM levels (80%) returned to their respective reference intervals. During this study, a faint monoclonal band was discovered in each of two patients. One had a normal baseline serum protein electrophoretogram before initiation of PE therapy, and the gammopathy was of uncertain significance. In the other patient, a vertebral plasmacytoma was discovered. It is concluded that PE reduces IgG, IgA, and IgM by approximately the same percentages; however, reference interval levels of IgA and IgM are restored more rapidly than IgG levels. Because monoclonal proteins may be present before or may appear during PE therapy, patients should be monitored by baseline and subsequent periodic serum protein electrophoresis.