Plasmapheresis is an established method to treat patients with large monoclonal gammopathies (M-components) that increases the blood viscosity. During plasmapheresis the patient plasma is substituted with a mixture of saline, albumin and normal plasma. The treatment results in a reduction of the M-component in the circulation. Plasmapheresis causes changes in several proteins, which makes monitoring by nephelometric or turbidimetric analysis of specific proteins less suitable. Quantification of paraproteins by nephelometric assays are also known to be associated with technical problems. An alternative could be agarose gel electrophoresis but this method is too slow to permit monitoring during the plasmapheresis. Capillary electrophoresis of plasma proteins can be performed in less than 10 min. We have used the CAPILLARYS TM capillary electrophoresis system (Sebia, Paris, France) to monitor the effect of plasmapheresis treatment on 22 occasions. The mean reduction in M-component size was 51%, range 33–61%. Capillary electrophoresis is a rapid and inexpensive method that could be used to monitor the effect of plasmapheresis during the actual treatment.