Interferon beta-1a and -1b reduce the frequency and severity of clinical exacerbations, and reduce both T2-weighted and contrast-enhanced MRI activity in patients with multiple sclerosis (MS). Several recent reports suggest that at the initiation of treatment there may be transient worsening of symptoms associated with the induction of interferon gamma-secreting cells. We studied eight MS patients with weekly brain MRI's after starting interferon beta treatment, and found immediate reduction in the number of contrast-enhancing lesions. Several patients did experience recurrence of previous symptoms without concomitant opening of the blood brain barrier on contrast-enhanced MRI. These data suggest that the symptoms described after the initiation of interferon beta are not associated with new disease activity, but rather may be related to preexisting lesions. This has implications for both understanding the immunopathogenesis of the disease and for its treatment.