The options for treating steroid unresponsive relapses in relapsing remitting multiple sclerosis (RRMS) are modest. We present a small series of patients with an aggressive course of RRMS whose steroid unresponsive relapses were treated with plasma exchange. In the period from January 2007 until February 2009 we identified four patients with steroid unresponsive relapses. All recorded relapses were treated with methylprednisolone, either with 500 mg for 5 days or 1000 mg for 3 days. If there was no improvement, patients were given five cycles of plasma exchange. If there was no recovery after the initial five cycles, five more were administered. Each patient's clinical status was monitored using the extended disability status scale. The median time from symptom onset until starting plasma exchange was 30 days (23-45 days). For four relapses, five cycles of plasma exchange were given with marked recovery in one, moderate in two, and mild in one case. In one patient, after five cycles there was no recovery, so five more cycles were administered, after which a moderate recovery ensued. This study further supports the efficacy of plasma exchange in the treatment of steroid unresponsive relapses in aggressive RRMS.