Improvement in exercise capacity may not be associated with significant changes in resting pulmonary haemodynamics. The present prospective study documented the relationships between improvement in 6-min walking distance (6MWD) and changes in resting and exercise pulmonary haemodynamics after treatment in patients with idiopathic pulmonary arterial hypertension (IPAH). A total of 42 IPAH patients underwent supine submaximal exercise haemodynamic assessments at baseline and after 5+/-2 months of therapy. The 6MWD, the corresponding chronotropic response (peak minus resting heart rate), and resting and exercise haemodynamic variables were analysed. The isoflow was defined as the lowest of the pre- and post-treatment peak cardiac index (CI). The extrapolated isoflow mean pulmonary artery pressure ((pa)) was used to characterise changes in (pa)-CI regression lines following treatment. Patients were given bosentan (n = 28), epoprostenol (n = 12) or both. The 6MWD increased significantly, from 399+/-88 to 442+/-86 m. On univariate analysis, changes in 6MWD correlated with changes in isoflow (pa), chronotropic response, resting haemodynamics (CI, pulmonary vascular resistance and mixed venous oxygen saturation) and exercise haemodynamics (peak CI). On multivariate analysis, only changes in isoflow (pa) and chronotropic response were independently associated with changes in 6MWD. Improvement in exercise tolerance with chronic therapy is independently related to improvement in pulmonary haemodynamics measured in exercise but not in resting conditions.