Treatment of patients with secondary pulmonary hypertension has been unsatisfactory. To describe exercise capacity, functional class, and hemodynamic variables after long-term intravenous infusion of prostacyclin in patients with secondary pulmonary hypertension. Case series. Academic referral center. 33 patients with secondary, precapillary pulmonary hypertension (New York Heart Association class III or IV). Continuous intravenous prostacyclin administered by portable infusion pump on a compassionate-use basis. Functional class, treadmill time, and hemodynamic variables. Patients were followed for an average of 12.7 +/- 5.6 months. Exercise tolerance and New York Heart Association class improved in each patient. The duration of treadmill exercise increased from 186 seconds to 491 seconds, an increase of 305 seconds (95% CI, 194 to 417 seconds; P < 0.001). Mean pulmonary artery pressure decreased from 60 mm Hg to 46 mm Hg, a decrease of 14 mm Hg (CI, 9 to 19 mm Hg; P < 0.001). Cardiac output increased from 3.90 L/min to 6.30 L/min, an increase of 2.40 L/min (CI, 1.56 to 3.25 L/min; P < 0.001). The pulmonary vascular resistance decreased from 1143 dynes x s/cm5 to 575 dynes x s/cm5, a decrease of 567 dynes x s/cm5 (CI, 407 to 727 dynes x s/cm5; P < 0.001). Patients with collagen vascular disease, congenital heart disease, and portopulmonary hypertension were analyzed with other patients and separately. All groups had a statistically significant reduction in mean pulmonary artery pressure and a statistically significant increase in cardiac output. Intravenous prostacyclin may be effective in the treatment of patients with certain types of secondary pulmonary hypertension.