BACKGROUND: Recent air travel recommendations suggest patients with precapillary pulmonary hypertension (PCPH) in New York Heart Association (NYHA) functional class 3 and 4 should have in-flight oxygen without the need for pre-flight testing. However it remains unclear as to how best to determine patients fitness to fly. METHODS: This study (i) investigates the effect of hypoxic challenge testing (HCT) on the arterial oxygen levels in a cohort of 36 patients with PCPH and (ii) compares the relative frequency with which FC and HCT predict the requirement for in-flight oxygen. RESULTS: The degree of arterial hypoxaemia induced by HCT (fall in partial pressure of oxygen in arterial blood (PaO(2)) 2.36 kPa, 95% CI 2.06-2.66 kPa) was similar to the drop observed in other published studies of chronic respiratory diseases. Following current air travel recommendations based on FC, 25 patients of the cohort would require in-flight oxygen whilst 10 subjects failed the HCT. Fourteen subjects had flown post-diagnosis. Of these, nine subjects should have had in-flight oxygen based on FC but were asymptomatic without. Also one who passed the HCT had developed symptoms during the flight whilst three who failed the HCT were asymptomatic flying without in-flight oxygen. CONCLUSIONS: Hypoxaemia induced by simulated air travel in patients with PCPH is similar to that seen in published studies of patients with other chronic respiratory diseases. HCT failed to predict correctly who had developed symptoms during an aircraft flight in a significant minority of the study subjects. Similarly guidelines based on functional class result in a major increase in the proportion of patients being advised to use oxygen, many of whom had been asymptomatic on previous flights without it. More work is required to improve prediction of need for in-flight oxygen in patients with PCPH.