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This article examines the International High Altitude Expedition of 1935 and its significance in the life and science of Ancel Keys. Both the expedition and Keys’s story afford excellent opportunities to explore the growing reach of interwar physiology into extreme climates—whether built or natural. As IHAE scientists assessed human performance and adaptation to hypoxia, low barometric pressure, and cold, they not only illuminated the physiological and psychological processes of high altitude acclimatization, but they also drew borderlines between the normal and the pathological, paved the way for the neocolonial exploitation of natural and human resources in Latin America, and pioneered field methods in physiology that were adapted and adopted by the Allied Forces during the Second World War. This case study in the physiology of place reveals the power and persistence of environmental determinism within biomedicine well into the twentieth century.