In order to test the hypothesis of whether strenuous physical exercise inhibits neutrophils which can get activated by hypobaric hypoxia, we analysed the effects of high altitude and strenuous exercise each alone and in combination on potentially cytotoxic functions of granulocytes in healthy volunteers (n=12, male, average age 27.6 yrs, range: 24-38). To this end a field study was prospectively performed with an open-labeled within-subject-design comprising three protocols: Protocol I (high altitude): helicopter ascent, overnight stay at 3196 m, and descent on the following day. Protocol II (physical exercise): hiking below an altitude of 2100 m with repetitive ascents amounting to a total ascent to that of Protocol III; Protocol III (combination of physical exercise and high altitude): climbing from 1780 m to 3196 meter, stay overnight and descent on the following day. In Protocol I, number of granulocytes did not change but potentially cytotoxic functions of cells (CD18 expression and superoxide production) were early and significantly upregulated. In Protocol II, subjects developed granulocytosis but functions of cells were inhibited. In Protocol III, granulocytosis occurred at higher values than those observed under Protocol II. Potentially cytotoxic functions of cells, however, were strongly inhibited again. Conclusions: High altitude alone, even moderate in extent, can activate potentially cytotoxic functions of circulating granulocytes. Strenuous physical exercise strongly inhibits this activation, which may protect from otherwise inflammatory injury.