To describe and treat a relapse of relapsing-remitting multiple sclerosis occurring during escalating therapeutic plasma exchange for a previous relapse. A 47-year-old woman with relapsing-remitting multiple sclerosis received plasma exchange as escalating therapy for a severe prolonged steroid-refractory relapse. During plasma exchange the patient developed another relapse with new neurological symptoms. The newly occurring relapse responded convincingly to pulsed high-dose steroids. During escalating relapse treatment with plasma exchange a new relapse can occur and, where appropriate, treatment with pulsed steroids can be useful, even if the previous relapse was unresponsive to glucocorticoids.