To explore the hypothesis that acute exposure to altitude hypoxia and acute mountain sickness (AMS) are associated with the release of vasoactive eicosanoids, 10 adult subjects were studied at sea-level and after 1-8 days (H1-H8) of exposure to an altitude of 4350 m (Observatoire Vallot). Plasma concentrations of 6 eicosanoids were determined in peripheral venous blood samples by radioimmunoassay after extraction with cooled ethanol and chromatographic separation by HPLC. All subjects experienced symptoms of AMS. Maximal clinical scores were observed at H1 or H2. Symptoms were no longer noted at H8. Hypoxia induced a very large increase in plasma concentration of most eicosanoids; thromboxane B2 (TxB2) and leukotriene B4 (LTB4) were maximum at H1 and H2 (about 5 times the normoxic value); prostaglandins PGE2, 6-keto-PGF1 alpha and PGF2 alpha were maximum at H3 or H4 (about 2.5-5 times of normoxic value). All eicosanoids returned almost to normoxic values by H8. Vasoconstricting mediators were released mostly at the initial phase (H1, H2), vasodilating mediators becoming predominant thereafter (H3, H4). The time pattern of appearance in blood of mediators acting on vascular permeability was strikingly parallel to the clinical score of AMS. In conclusion, exposure to acute hypoxia induced a large increase in plasma concentration of eicosanoids, the variation with time of which is compatible with a hydrostatic-permeability hypothesis of AMS pathophysiology.