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In this study we introduced and tested the clinical efficacy of a combined treatment based on the association of plasma exchange (PE) with high daily doses of prednisone in 18 patients with severe forms of myasthenia gravis (MG). A myasthenic score based on strength and resistance was evaluated in each patient in basal condition and during the treatment. The study design included 5 sessions of PE, performed within a period of 15 days, 1 session every 3 days, associated with administration of oral prednisone (1 mg/kg of body weight), which began at the same time as the first session and was continued following a daily schedule for at least three months. A significant improvement was obtained from the start of the therapy, with a reduction of the myasthenic score from 26.56 to 11.44 by day 10 and with further reduction after PE interruption. An early improvement, recorded within 24-48 hours of the beginning of the study design, was observed in 11/18. The administration of steroid therapy was never followed by a worsening of myasthenic symptoms (as reported when it is administered in the absence of concomitant PE). No recurrence of symptoms was reported after 29 months' follow-up. This type of therapeutic association was generally well tolerated and no unwanted side effects were observed. According to our results we can conclude that medium-high doses of oral prednisone in simultaneous association with PE lead to a successful control of severe forms of MG and may be considered a valid therapeutic strategy.