There is evidence that pulmonary arterial hypertension plays a major role in the occurrence of high altitude pulmonary edema (HAPE). We tested the hypothesis that the pulmonary arterial systolic pressure response to a challenge associated with hypoxia and mild exercise may be considered a predictive factor of HAPE. Pulmonary arterial systolic pressure was measured by Doppler echocardiography in 8 HAPE susceptible (HAPE-S) subjects and 8 HAPE resistant mountaineers (HAPE-R) during a hypoxic exercise challenge established by the French Association for Sport Medicine (Richalet's test). Pulmonary arterial systolic pressure during hypoxic exercise allowed a significant discrimination between the groups, although an overlap of values was observed. When expressed as individual variations from baseline to hypoxic exercise level however, we found a highly significant difference. No overlap was observed between HAPE-R (range: 6.7-18.5 mmHg) and HAPE-S (range: 19.2-30.4 mmHg) groups, with a cut-off value at 19 mmHg. Plasma Vascular Endothelial growth factor (VEGF) and malondialdehyde (MDA) increased in response to hypoxic exercise only in HAPE-S group. Individual increases in pulmonary arterial systolic pressure during hypoxic exercise from basal resting normoxic values seem relevant to estimate HAPE susceptibility when measured during the Richalet's test.