Exposure to high altitude causes alveolar hypoxia and induces pulmonary hypertension (PH) with consequent limitation of exercise capacity. To assess the impact of sildenafil on haemodynamic and clinical parameters, and on aerobic performance, 12 young healthy unacclimatised subjects were studied (6 received sildenafil 40 mg t.i.d. and 6 received placebo) at sea level and high altitude. Systolic pulmonary artery pressure increased at high altitude, but normalised with sildenafil. The altitude-induced decrease in maximal O2 consumption was significantly smaller with sildenafil than with placebo. Enhancing pulmonary circulation with sildenafil safely protects against the high altitude-induced PH and improves gas exchange.