This commentary discusses a study by van der Voort et al. that tested the diagnostic value of in vivo interferon beta (IFN-beta) bioactivity screening in identifying patients with multiple sclerosis who have developed neutralizing antibodies (NAbs) to IFN-beta therapy--an event that limits the efficacy of the therapy. The in vivo assay used by the authors, which measures expression of the IFN-beta-stimulated gene MxA (MX1) in the peripheral blood, indicated lack of a biological response in 19 of 23 patients with high-titer NAbs following injection of IFN-beta. However, an abnormal response was also observed in 18 of 55 patients who had low-titer NAbs or were NAb negative. The authors concluded that in patients treated with IFN-beta a single postinjection measurement of MxA messenger RNA expression is adequate to determine the IFN-beta bioactivity status. While we believe that in vivo measurement of MxA messenger RNA following IFN-beta injection is a reliable test by which to identify patients with inadequate response to IFN-beta, the capacity of the test to predict treatment failure must be established in a well-designed, prospective trial.