Three fish species with different strategies for anoxic survival (goldfish, tilapia, and common carp) were exposed to environmental anoxia (4, 3, and 1 h, respectively). The concentrations of high energy phosphate compounds and inorganic phosphate, besides the intracellular pH in the epaxial muscle were measured during anoxia and recovery by in vivo 31P NMR spectroscopy. The concentration of free ADP was calculated from the equilibrium constant of creatine kinase. During anoxia the patterns of phosphocreatine utilization and tissue acidification are remarkedly similar. Free ADP rises rapidly during the initial period of oxygen deficiency and reaches a plateau in goldfish and tilapia, while it keeps rising in the common carp. At elevated levels of free ADP, the creatine kinase reaction and anaerobic glycolysis are functionally coupled by H+ as a common intermediate. The coupling between both processes disappears upon reoxygenation, when mitochondrial respiration induces a rapid drop of [free ADP]. The removal of ADP shifts the creatine kinase equilibrium toward phosphocreatine synthesis despite the low pH.