Generalized scleroderma (GS) is associated with dysimmunity anomalies suggesting possible benefits of plasma exchange (PE) therapy. Nineteen patients with GS were treated by PE (volume of plasma exchange equivalent to 5-6% body weight and replacement by 4% human albumin), initially three times weekly, then weekly, bi-monthly and monthly (total duration 12-18 months). Clinical and paraclinical follow up was for an average of more than 2 years after the end of PE (mean number 17 per patient). Clinical results were assessed as positive and lasting in 11 cases (57.9%), two cases remaining stable and three cases worsening (one death from heart failure). The remaining three cases were failures in application of treatment (difficult venous approach). Improvement was noted in cutaneous sclerosis (62% of cases), trophic disorders (recovery in 6 of 7 cases) and articular manifestations. Vasomotor disorders were improved in only 20% of cases and visceral lesions unaltered. Results of capillaroscopy showed improvement in 5 of 11 cases. Biological values could not be correlated with either the course or the therapeutic efficacy. General tolerance to PE was good but the venous approach must be of good quality. These findings suggest the need for a randomized trial to define the place of PE in the treatment of GS.