Pulmonary arterial hypertension (PAH) is an uncommon but devastating disease. There is increasing evidence of a correlation between interferon (IFN) use and PAH. Very few cases of PAH in patients treated with IFN are reported in literature. We report a case of a 47-year-old woman with previous diagnosis of multiple sclerosis treated with IFN β-1a for 6 years, presenting severe respiratory failure (paO2/FiO2 228) because of pulmonary hypertension. The suspension of the drug along with the treatment of PAH improved the clinical picture allowing cessation of oxygen administration. Pathophysiological effects of IFN on endothelial vascular cells are discussed.