The purpose of this study was to analyse the ventilatory efficiency for carbon dioxide (CO2) in the assessment of exercise tolerance in patients with pulmonary hypertension. Two groups of patients were studied. One group consisted of 37 patients with normal pulmonary artery pressure who underwent surgical closure of a left-to-right shunt. Another group was composed of 10 patients with pulmonary hypertension. Both patient groups were compared with the mean value of an age-matched pool of normal control subjects. Aerobic exercise performance was assessed by determination of the ventilatory threshold. The ventilatory efficiency for CO2 was assessed by calculating the slope of ventilation over carbon dioxide below the ventilatory threshold. The slope of ventilation vs. carbon dioxide output in patients with pulmonary hypertension (48 +/- 12) was steeper than the slope (31.3 +/- 7.0) in patients with normal pulmonary artery pressure (P < 0.05). Significant correlations (P < 0.05) were found between the pulmonary artery pressure and the slope of pulmonary ventilation over carbon dioxide (r = 0.92) and also with the physiological dead space-tidal volume ratio at maximal exercise (r = 0.55). This was associated with a severe reduction in exercise performance in patients with pulmonary hypertension, whereas in patients with normal pulmonary artery pressure it was only slightly below the lower limit of normal. These results demonstrate that patients with pulmonary hypertension have an inefficient ventilatory response to metabolically produced CO2 during exercise, which severely limits exercise tolerance.