Multiple coagulation studies were carried out in eight healthy young men at sea level (SL) and after 1, 24, and 48 h at a simulated altitude of 4,400 m. Platelet aggregation, as induced by ADP, epinephrine, and collagen, was not significantly altered by high-altitude (HA) exposure. Mean 2,3-diphosphoglycerate, a physiological inhibitor of platelet aggregation, rose (P less than 0.001) after 24 h at HA and remained elevated while no changes in circulating catecholamines were observed. Platelet count, factor 3 availability, and membrane lipid peroxide formation were likewise unaltered at HA, as were prothrombin and thrombin times and protamine paracoagulation test. However, mean partial thromboplastin time was significantly shortened (P less than 0.01) after 1 and 24 h at HA, recovering to SL control by 48 h. Fibrinogen and factor VIII levels also fell (P less than 0.01 and P less than 0.02) after 1 h at HA but returned to the preexposure values by 24 h. Fibrin degradation products were transiently detectable in three subjects at HA. Thus, although normal platelet function did not appear to be modified by short-term exposure to simulated high altitude, evidence for a coagulopathy was obtained.