BACKGROUND: The oral dual endothelin (ET) antagonist bosentan has been established as a cornerstone in the treatment of pulmonary arterial hypertension (PAH). ET is believed to be a key pathogenic mediator in systemic sclerosis (scleroderma, SSc), causing fibrotic, hypertrophic and inflammatory processes. PAH is one of the resulting deleterious effects in approximately 15% of SSc patients. MATERIALS AND METHODS: This was an open-label prospective observational study of 8 patients aged 34-73 years with symptomatic, severe PAH related to SSc (WHO class III or IV) and mostly, lung fibrosis. PAH diagnosis was ascertained with echocardiography or right heart catheterization. Patients were treated on top of diuretics and anticoagulants with bosentan 62.5 mg twice daily for 4 weeks followed by a maintenance dose of 125 mg twice daily. RESULTS: The mean 6-minute walk distance (data available in 7 patients) increased from 71.9 (+/- 54.7) m at baseline to 191.9 (+/- 104.6) m after 3 months (P = 0.012) and to 202.6 (+/- 108.1) m after 6 months (P = 0.011), respectively. Six of 8 patients improved in the 6-minute walk test, and these 6 patients also improved in World Health Organization functional class. Two patients did not sufficiently respond to bosentan therapy; one of them died. The tolerability of bosentan was good, and there were no discontinuations. Elevations of hepatic aminotransferases above 3 times the upper limit of normal were not recorded. CONCLUSION: Bosentan treatment was well tolerated in this cohort of SSc patients with interstitial lung disease and was effective for treatment of severe PAH in the majority of patients.