The primitive atmosphere where aerobic life started on earth was hypoxic and hypercapnic. Remarkably, an adaptation strategy whereby O(2) partial pressure, P(O(2)), in the arterial blood is maintained within a low and narrow range of 1-3 kPa, largely independent of inspired P(O(2)), has also been reported in modern water-breathers. In mammalian tissues, including brain, the most frequently measured P(O(2)) is in the same low range. Based on the postulate that basic cellular machinery has been established since the early stages of evolution, we propose that this similarity in oxygenation status is the consequence of an early adaptation strategy which, subsequently throughout the course of evolution, maintained cellular oxygenation in the same low and primitive range independent of environmental changes. The rational for such an evolutionary theory is discussed in terms of an equilibrium between physiological and pathological reactions associated with O(2) excess vs O(2) lack and emerging concepts about the importance of cellular O(2)-dependent mechanisms in the low but physiological P(O(2)) range.