The ability to treat selected patients with obliterative pulmonary hypertension (OPH) with vasodilator therapy has been clearly demonstrated. However, the dangers involved in their use in patients who fail to have a beneficial response have also been well documented. A major problem in the management of these patients has been the lack of an easily measurable, noninvasive index of alterations in cardiopulmonary status that could be used at relatively frequent intervals to monitor the response to therapy. We have studied the utility of changes in noninvasively assessed exercise performance to predict changes in pulmonary vascular tone. In 10 patients with OPH, we compared symptom-limited oxygen consumption (Vo2ex) and oxygen pulse (Vo2/heart rate) at Vo2ex (O2 Pex) determined during progressive treadmill exercise with invasive measurements of cardiovascular function during steady-state supine bicycle submaximal exercise prior to and 8 wk after initiation of vasodilator therapy with nifedipine or diltiazem. After vasodilator therapy, total pulmonary vascular resistance decreased at rest and during exercise in 6 patients. At the same time, changes in Vo2ex ranged from -33 to 47% and in O2Pex from -26 to 57%. There was an excellent relationship between the magnitude of the change in exercise and resting total pulmonary vascular resistance and the change in both Vo2ex and O2Pex. We suggest that changes in Vo2ex and O2Pex may be a useful means of following the ability of vasodilators to improve cardiovascular function in patients with OPH.