The development of neutralizing antibodies (NAbs) to interferon (IFN) is a common phenomenon of IFN beta therapy for relapsing-remitting multiple sclerosis (RRMS) patients. Here we examine the specificity of NAbs developed during therapy for RRMS with recombinant interferon (rIFN) beta-la or rIFN beta-1b, and study the effect of switching from rIFN beta-la to rIFN beta-1b on the incidence and specificity of NAbs. The relative ability to neutralize rIFN beta-Ia and beta-1b was assayed in sera positive for NAbs derived from RRMS patients treated with either rIFN beta-la (N=9) or rIFN beta-lb (N=16), while the incidence and specificity of NAbs to IN beta developed during therapy were studied in 50 RRMS patients who were treated for two years with rIFN beta-la followed by a further year either switching to rIFN beta-1b (N=34) or continuing treatment with rIFN beta-1a (N=16). The results show that all positive sera, independent of the source, may recognize both forms of rIFN beta and that a further year of treatment does not significantly affect the incidence and specificity of the NAbs developed during the first two years of treatment even if treatment is switched to a different type of IFN beta. The data then suggests that it is unlikely that the administration of rIFN beta-1b to anti-rIFN beta-la NAbs-positive patients can overcome the inhibitory effect exerted by the serum antibodies land vice versa), and that a further period of treatment with IFN beta-ib in patients previously treated with rIFN beta-la does not significantly change the pattern of antibody response to IFN beta. (C) 1999 Elsevier Science B.V. All rights reserved.