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There is no known disease-modifying therapy for progressive systemic sclerosis.It was shown that a patient with secondary fibromyalgia syndrome for whom the development of systemic sclerosis was suspected because of a Raynaud's phenomenon and the presence of SCL-70 antibodies in the serum had experienced a clear pain reduction under treatment with tropisteron, which is the reason why this drug was also used with established systemic sclerosis.Two patients with progressive systemic sclerosis and positive SCL-70 antibodies were treated for 6 weeks with 5 mg tropisetron daily. Both patients had clear skin symptoms, functional impairments of the locomotor system, and a secondary fibromyalgia syndrome. The skin score and joint motion were checked before, during, and after treatment. In addition, the patients filled in the visual analog scale for pain at these times. At the end of the 6 weeks, the patients showed a clear improvement of the skin score and the movability of various joints as well as a clear reduction of pain. The medication was well-tolerated. Constipation developed in the patients; it could be controlled with laxatives. Follow-up questioning of the patients after 3 months showed that their condition had remained stable.Two patients with progressive systemic sclerosis showed an improvement of various symptoms under a blockade of the 5-HT3 receptors via tropisetron. The long-lasting effect pointed to immunomodulation. The two cases give cause for clarifying this by means of clinical studies, which should also investigate the question of dosage (possibly 5 mg tropisetron twice daily).