To determine whether low-dose prednisone reduces flu-like symptoms at the initiation of interferon beta 1-b (IFNbeta-1b), we studied 71 patients with clinically definite, relapsing-remitting multiple sclerosis who were started on IFNbeta-1b. Patients were randomized to receive prednisone plus paracetamol or only paracetamol and were monitored for side effects. Systemic side effects were minimal in the steroid group compared with the nonsteroid group during the first 15 days of treatment (p=0.005). At 3 months, both groups showed a similar frequency of flu-like symptoms. No differences in local reaction between the two groups were observed throughout the study.