Oxygen deficit is not simply a pathophysiological incident but is at the same time a physiological event. Adaptations to high altitude or physical endurance exercise are examples of "physiological oxygen deficit". Pathophysiological conditions, on the other hand, are associated with reduced cerebral or cardiac circulation or blood loss. One of the cardinal issues of crucial importance, in this context, is relating to the nature of the "oxygen deficit sensor" which, for example, leads to increased expression of hematopoietic hormones (erythropoietin) or angiogenesis factors (Vascular Endothelial Growth Factors, VEGF). Molecular principles of such oxygen sensors are accurately defined only for certain systems: In the case of erythropoietin, only one fully known section in the 3'-region of the erythropoietin gene is necessary and is sufficient to "transfer" O2-sensitivity to that particular gene. Nuclear proteins (transcription factors), controlled by O2-deficit, are of decisive importance to that process. Additional findings are likely to suggest that a DNA section closely similar to the one regulating the VEGF gene is encoding for hypoxia dependence. In other systems, above all in the central nervous system, there are ATP-dependent Na+ or K+ flows protecting the neurons against oxygen deficit. Drop in intracellular ATP-concentration is followed by hyperpolarization of neurons due to increases in K(+)-conductivity or due to decreases in stress-dependent Na(+)-channels, with both of them apparently ATP-controlled.(ABSTRACT TRUNCATED AT 250 WORDS)