Primary pulmonary hypertension and pulmonary hypertension associated with collagen vascular disease or HIV infection are rapidly progressive fatal diseases in spite of conventional medical therapy. Continuous intravenous infusion of prostacyclin has been shown to prolong life in severe primary pulmonary hypertension, and aerosolised prostacyclin has been used successfully on a short-term basis in patients with pulmonary hypertension. We investigated the effects of acute administration of aerosolised prostacyclin or its analogue iloprost in 5 patients with severe pulmonary hypertension; 4 of these patients were followed over a period of 7 months. On acute testing, mean pulmonary artery pressure decreased from 59 to 46 mm Hg (p = 0.01); echocardiographically estimated systolic pulmonary pressure further declined from 66 mm Hg after 2 days' treatment to 54 mm Hg after 7 months (p = 0.03). Symptom-limited walking distance significantly improved from 42 to 87 m after 2 days' treatment (p = 0.003); a further 2- to 8-fold increase was observed in single patients during follow-up. In severe pulmonary hypertension, aerosolised prostacyclin or iloprost improves exercise capacity and lowers pulmonary artery pressure beyond the level achieved on acute exposure.