There are no reliable predictors of mortality in primary pulmonary hypertension (PPH). This study assessed whether exercise oxygen desaturation and distance achieved during a six-minute walk are associated with mortality in moderately symptomatic patients with PPH. Thirty-four patients with PPH underwent a pretreatment six-minute walk test, and an invasive haemodynamic assessment of pulmonary vasodilator reserve, to select the best treatment option (epoprostenol in 27 and nifedipine in 7). Median follow-up was 26 months (12 months for the nonsurvivors was 26%), and median survival, >46 months by Kaplan-Maier estimate. The mean+/-SD distance walked was 275+/-155 m and reduction in arterial oxygen saturation (Sa,O2) at maximal distance (deltaSa,O2) was 8.4+/-4.5%). A distance < or =300 m increased mortality risk by 2.4, and a deltaSa,O2 of > or = 10% increased mortality risk by 2.9. Only Sa,O2 at peak distance, deltaSa,O2 and pulmonary vascular resistance (PVR) were related to mortality. After adjusting for PVR, there remained a 27% increase in risk of death for each per cent decrease in Sa,O2. The six-minute walk distance and exercise oxygen saturation may be helpful in selecting patients with primary pulmonary hypertension for whom transplant listing is appropriate.