Oxygen is essential for all higher forms of animal life. It is required for
oxidative phosphorylation, which forms the bulk of the energy supply of mo
st animals. In many vertebrates, transport of O-2 from respiratory to other
tissues, and of CO2 in the opposite direction, involves red cells, These a
re highly specialised, adapted for their respiratory function. Intracellula
r haemoglobin, carbonic anhydrase and the membrane anion exchanger (AE1) in
crease the effective O-2- and C-2-scarrying capacity of red cells by approx
imately 100-fold. O-2 also has a pathological role. It is a very reactive s
pecies chemically, and oxidation, free radical generation and peroxide form
ation can be major hazards. Cells that come into contact with potentially d
amaging levels of O-2 have a variety of systems to protect them against oxi
dative damage. Those in red cells include catalase, superoxide dismutase an
d glutathione. In this review, we focus on a third role of O-2, as a regula
tor of membrane transport systems, a role with important consequences for t
he homeostasis of the red cell and also the organism as a whole. We show th
at regulation of red cell transporters by O-2 is widespread throughout the
vertebrate kingdom. The effect of O-2 is selective but involves a wide rang
e of transporters, including inorganic and organic systems, and both electr
oneutral and conductive pathways. Finally, we discuss what is known about t
he mechanism of the O-2 effect and comment on its physiological and patholo
gical roles.