It is commonly thought that people are at increased risk of venous thrombosis during air flights, but the magnitude of the risk is unknown. Suggested risk factors are hypobaric hypoxia, stasis, and dehydration. In a previous experimental study, we found immediate activation of coagulation as determined by the levels of prothrombin fragments 1 + 2 (F(1 + 2)) and thrombin-antithrombin complex (TAT) after rapid exposure to a hypobaric and hypoxic environment (76 kPa). The aim of the present study was to examine the ability of low molecular weight heparin (LMWH) to prevent such activation. Twelve healthy male volunteers were given 40 mg enoxaparin as a single subcutaneous injection 1 h prior to exposure from 96.3 to 76 kPa. We found no activation of coagulation as judged by F(1 + 2) or TAT. Anti-activated factor X activity levels and release of tissue factor pathway inhibitor was normal. We conclude that high prophylactic doses of a LMWH most probably prevent activation of coagulation in a hypobaric environment.