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Symptoms and signs of infectious disease are increased in subjects at altitude. Most infections at altitude are diagnosed clinically and do not have objective data to support the diagnosis. Since in vivo innate immune responses to hypoxia have not been thoroughly characterized, we investigated the effect of acute systemic hypocapnic hypoxia on leukocyte trafficking and neutrophil activity in healthy humans at rest.Sixteen male subjects [mean +/- SD age 28.3 +/- 6.5 yrs, body mass 80.9 +/- 15.9 kg, Vo2peak 4.10 +/- 0.76 L x min(-1)] breathed a hypoxic gas mixture (F(IO)2 = 12.2%, equivalent to 4000 m; H) or normoxic room air (F(IO)2 = 20.9%; N) for 240 min, via a mouthpiece, followed by 60 min of normal breathing.H induced a differential response in peripheral venous blood neutrophils (p0.05), lymphocytes (p0.01), and eosinophils (p0.01; 60-240 min), resulting in a relative lymphopenia (H 1.88 +/- 0.48 and N 2.14 +/- 0.45 x 10(9) L(-1)) and neutrophilia (H 5.2 +/- 1.8 and N 3.9 +/- 1.1 x 10(9) L(-1)) by 240 and 300 min, respectively. Unstimulated leukocyte oxidative activity, as determined by luminol enhanced chemiluminescence; plasma elastase, a marker of in vivo neutrophil degranulation; and sP-selectin, a marker of endothelial cell activation, did not change throughout.Differences in immune cell numbers showed a marked similarity to changes previously reported in response to intense short- and long-duration exercise and were attributed to the physiological responses induced by acute hypoxia that are known to mediate immune cell trafficking. These findings could be relevant to the etiology of conditions where hypoxia and immune cells are implicated.