We have previously demonstrated that prophylactic intake of dexamethasone improves maximal oxygen uptake (Vo(2)max) in high altitude pulmonary edema (HAPE) susceptible subjects 4 to 6 h after a 2-day climb to 4559 m. However, since with this ascent protocol HAPE usually develops after the first night at 4559 m or later, we hypothesized that a continued dexamethasone prophylaxis would result in an even more pronounced improvement of Vo(2)max after an additional night at high altitude. Vo(2)max of 24 HAPE susceptibles was evaluated on a bicycle ergometer at an altitude of 490 m and at 24 h after rapid ascent to 4559 m. Subjects were divided into two groups: The control group (n=14) performed both tests without dexamethasone, whereas the dexamethasone group (n=10) received dexamethasone 8 mg twice a day (b.i.d), starting 24 h prior to ascent. At 4559 m, Vo(2)max was 61% ± 6% of the baseline value in the control group and 70% ± 9% in the dexamethasone group (p=0.025). Similarly, O(2) pulse (Vo(2)/heart rate) was 68% ± 7% and 77% ± 11% of baseline, respectively (p=0.043). Arterial O(2) saturation at maximal exercise did not differ between groups, whereas at rest it was 83% ± 10% in the control group and 91% ± 4% in the dexamethasone group (p=0.009). Dexamethasone prophylaxis increased Vo(2)max of HAPE-susceptible individuals after the first night at 4559 m without affecting arterial O(2) saturation at maximal exercise. This might be explained by a sustained effect of dexamethasone on maximal cardiac output and pulmonary O(2) diffusion, both resulting in enhanced convectional O(2) transport to the locomotor muscles.