Recent clinical trials with interferon-beta (IFN-beta) in relapsing-remitting multiple sclerosis (RRMS) have clearly demonstrated that the IFN-beta dosing regimen affects the clinical efficacy, thereby highlighting the importance of determining the relative biologic activities of the IFN-beta products currently available. Although studies have been published that examine the biologic activities of the two structurally different forms of recombinant IFN-beta, IFN-beta1a (Rebif), Serono, Geneva, Switzerland) and IFN-beta1b (Betaseron)/Betaferon), Berlex [Montville, NJ]/Schering [Berlin, Germany]), there have been few direct comparative studies. Therefore, to obtain a more accurate estimate of the relative biologic activities of Rebif and Betaseron, this study examined the antiviral activities of these two products within the same assay system and against the same natural human IFN-beta standard. Whereas the manufacturers' information suggests that the bioactivity of Betaseron is only about 8.7-fold less than that of Rebif, the results of the present direct, comparative study show that Rebif has an antiviral activity 14 times greater than that of Betaseron. This may have important clinical implications, because on the basis of the results reported here, Rebif at 44 microg t.i.w. is approximately double the maximal licensed weekly dose for Betaseron.