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Back ground and purpose. The development of neutralizing antibodies (NAbs) against interferon beta (IFN-β) during IFN-β treatment in multiple sclerosis (MS) patients has been a significant clinical problem. Persistent, high-titer NAbs-IFN-β reduce or eliminate biological activity of IFN-β therapies for MS and are associated with reduction in efficacy. Therapeutic plasma exchange (TPE) removes the circulating antibodies that are thought to be active in the diseases, so we hypothesized that TPE can restore the ability of IFN-β to induce the Myxovirus Resistance Protein A (MxA) mRNA expression and the maintenance plasmapheresis can sustain the bioavailability of IFN-β. Methods. Eligible patients under went primarily four separate plasma exchange sessions and after the induction TPE sessions they were transferred to the maintenance plasma pheresis. Bioactivity of interferon beta was expressed as in vivo MxA mRNA induction in whole blood using real time PCR. Results. Six patients with RRMS and low IFN-β bioavailability detected by the MxA mRNA response were included. Four patients after induction plasmapheresis be came biological responders. In two patients an in crease of MxA mRNA expression was found, but the values persisted be low the cut-off and the patients remained as "poor biological responders". The effect of maintenance plasmapheresis was quite transient: MxA mRNA expression values reverted to the base line levels after one or two months. Conclusion. Plasma exchange may restore the bioavailability of IFN-β in some patients, but the effect of maintenance plasmapheresis on the bioavailability of IFN-β is transient. [ABSTRACT FROM AUTHOR]