We have examined the hypothesis that hypoxaemia contributes to breathlessness by a mechanism distinct from its action as a ventilatory stimulant. Five patients who developed arterial oxygen desaturation during incremental exercise were studied. Exercise tests were performed on a cycle-ergometer. Breathlessness was measured by using a visual analogue scale technique. All five patients had considerable previous experience of these procedures. Two identical exercise tests were performed by each patient, breathing either room air or 60% oxygen in a blind randomized study. Breathing air, arterial saturation at rest was 93% and fell by 7% during exercise. Breathing 60% oxygen, resting saturation was 98% and there was no fall during exercise. Breathing oxygen, ventilation for a given work load was reduced and exercise duration was increased when compared with air breathing. In each of the five patients the relationship between breathlessness and minute ventilation was the same whether breathing air or 60% oxygen, despite the reduction in ventilation for a given work rate.