After exhaustive exercise the muscular store of creatine phosphate (CP) is almost completely depleted. The resynthesis of CP during recovery normally occurs rapidly, but is totally inhibited if the local circulation to the muscle is occluded. The limiting factor for CP resynthesis which could be a low intramuscular pH or availability of oxygen has been investigated in the present study. Biopsies from musculis quadriceps femoris of man were analyzed for pH, ATP, ADP, CP, creatine, lactate and pyruvate. It was shown that resynthesis of CP only occurs when the blood supply to the muscle is intact. From this it was concluded that the creatine kinase reaction is at a steady state or at equilibrium during the period of recovery. The influence of oxygen on the resynthesis of CP was investigated by incubating muscle samples taken after a fatiguing isometric contraction in atmospheres of oxygen and nitrogen, respectively. During 15 min incubation in oxygen CP was resynthesized from a starting value of 4% to 68% of the normal value at rest. No resynthesis was observed when parallel muscle samples were incubated for the same time in nitrogen. It is suggested that the initial fast phase of CP resynthesis is limited by the availability of oxygen whereas the subsequent slow phase is limited by the hydrogen ion transport out from the muscle.