Although the exact etiology of progressive systemic sclerosis (SSP) is still unknown, it is felt that immunologic disorders may be implicated in its pathogenesis. On the basis of these considerations, an open study with an immunomodulating drug, thymopentin, was performed in 20 SSP outpatients. These subjects were initially treated with thymopentin three times a week for three consecutive months (phase I); during a second study phase lasting three months, 10 patients continued to receive thymopentin and the remaining 10 placebo (phase II). A significant improvement in various clinical, laboratory and instrumental findings was seen following thymopentin treatment. During phase II, those on placebo regressed to basal conditions, while an added improvement was noted in those who continued with thymopentin.