In this open pilot study, the potential therapeutic efficacy of Cyclosporin A (CsA) in systemic sclerosis (scleroderma) was investigated. Eight patients with severe scleroderma (skin manifestation and at least three organ manifestations such as pulmonary, intestinal, cardiac, renal, and severe hypertension) were included in the study. CsA administration was started at a dose of 5 mg per kg body weight per day and then, to obtain whole blood levels of 300-500 ng/ml, adjusted to a mean dosage of 4.3 mg/kg/day. Therapeutic effects were evaluated by monitoring the measures of cutaneous, pulmonary, cardiac, gastrointestinal, and renal involvement as well as laboratory parameters. After 6 to 12 months of CsA-administration, cutaneous abnormalities improved in seven, arterial oxygen tension slightly increased in four, pulmonary hypertension decreased in five, and smooth muscle esophageal contraction amplitudes improved in three patients. However, the disease progressed in one patient. No serious side effects were observed, and occurring renal side effects were mild. Taken together, these observations indicate that CsA administration may be effective mainly in the skin involvement, but also in some organ manifestations of scleroderma. The results of this pilot investigation therefore indicate that a controlled study of the efficacy of CsA in scleroderma is needed and ought to be performed.