The extent of exercise limitation and the mechanisms for that limitation in 11 patients with primary pulmonary hypertension (PPH) were studied by progressive, upright cycle ergometry. All patients had a mean pulmonary artery pressure of 30 mm Hg or higher (mean, 56 +/- 15), normal pulmonary function testing, normal pulmonary capillary wedge pressure, and pulmonary angiography consistent with the diagnosis. Rest and exercise data obtained from the patients with PPh were compared with data obtained from 11 matched, sedentary control subjects. Mean maximal oxygen consumption (VO2) was 13 +/- 4 ml/kg/min in the PPH group compared with 28 +/- 7 ml/kg/min in the controls. At maximal VO2 the minute ventilation (VE) was similar; however, the VE at any level of carbon dioxide production (VCO2) during rest and exercise was significantly higher in the PPH group. Maximal heart rate and oxygen pulse (VO2/heart rate) was significantly higher in the control group (148 +/- 18 vs 180 +/- 24, and 6.3 +/- 2.2 vs 9.9 +/- 3.9, respectively). Anaerobic threshold occurred earlier during progressive exercise in the PPH group and correlated positively with the maximal oxygen pulse achieved in patients with PPH. In conclusion, patients with PPH have severe exertional limitation due to cardiovascular factors with an inability to maintain appropriate oxygen delivery to the body during exercise. No respiratory impairment was recognized; however, an exaggerated ventilatory response to exercise at any level of VCO2 was found.