Owing to the variability of oxygen tension in aquatic, especially the freshwater environment, oxygen has been a major force in the evolution of fishes. Their long evolutionary history, and the present different oxygen requirements between species, and acclimatory responses to hypoxic and hyperoxic conditions make fishes prime models in the study of oxygen-dependent cellular functions and their regulation. In the present article oxygen-dependent membrane transport, cellular signalling, energy metabolism, gene expression and apoptosis are reviewed with an emphasis on available results on fish. Available data on oxygen sensing are described and examples on the cascade from sensing oxygen to its physiological effects are given. From the data it is clear that hitherto fish have not been utilised in the study of oxygen-dependent cellular regulation as much as their evolutionary history and present oxygen requirements would give possibilities to. Even more generally, oxygen has hitherto seldom been a carefully controlled key variable in experimental cell biology. (C) 2002 Elsevier Science Inc. All rights reserved.