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Aim To examine the response of brain natriuretic peptide ( BNP) and NT-pro BNP to high altitude ( HA) both at rest and following exercise. Methods We measured NT-pro BNP and BNP and Lake Louise ( LL) acute mountain sickness ( AMS) scores in 20 subjects at rest in Kathmandu ( Kat; 1300 m), following exercise and at rest at 4270 and 5150 m. Results BNP and NT-pro BNP (pg ml−1, mean ± SEM) rose significantly from Kat (9.2 ± 2 and 36.9 ± 6.6, respectively) to arrival at 4270 m after exercise (16.6 ± 4 and 152 ± 56.1, P = 0.008 and P < 0.001, respectively) and remained elevated the next morning at rest (28.9 ± 9 and 207.4 ± 65.1, P = 0.004 and P < 0.001 respectively). At 5150, immediately following ascent/descent to 5643 m, BNP and NT-pro BNP were 32.3 ± 8.8 and 301.1 ± 96.3 ( P = 0.003 and P < 0.001 vs. Kat, respectively) and at rest the following morning were 33.3 ± 9.7 and 258.9 ± 89.5 ( P = 0.008 and P = 0.001 vs. Kat respectively). NT-pro BNP and BNP correlated strongly at 5150 m (ρ 0.905, P < 0.001 and ρ 0.914, P < 0.001 for resting and post-exercise samples respectively). At 5150 m, BNP levels were significantly higher among the four subjects with severe ( LL score > 6) AMS (58.4 ± 18.7) compared with those without ( BNP 22.7 ± 8.6, P = 0.048). There were significant correlations between change in body water from baseline to 5150 m with both BNP and NT-pro BNP (ρ 0.77, P = 0.001, ρ 0.745, P = 0.002 respectively). Conclusion In conclusion, these data suggest that BNP and NT-pro BNP increase with ascent to HA both after exercise and at rest. We also report the novel finding that BNP is significantly greater in those with severe AMS at 5150 m. [ABSTRACT FROM AUTHOR]