Complex physiologic responses occur as nonacclimatized lowland dwellers ascend above 10,000 feet, with a resulting partial pressure of arterial oxygen of less than 60 mm Hg. There are marked hemodynamic changes and shifts in body fluids that may result in organ dysfunction. The suspected pathogenesis of these acute hypobaric hypoxic-induced illnesses is discussed. Cerebral dysfunction may present as acute mountain sickness or high-attitude cerebral edema. Usually asymptomatic high-altitude retinal hemorrhage and non-cardiogenic high-altitude pulmonary edema also are described. All of these illnesses apparently represent a spectrum of pathologic states initiated by an exaggerated vascular response to hypoxia. With the exception of retinopathy, high-attitude illness can be prevented by slow ascent. Early recognition of cerebral or pulmonary edema and immediate descent will prevent serious consequences of nonacclimatized persons who are acutely exposed to hypobaric environments.