Adenine nucleotide analysis of tissue and perfusates of the isolated rabbit heart were undertaken following hypoxia and uncoupled oxidative phosphorylation. During uncoupled oxidative phosphorylation, nucleotide degradation, primarily that of ATP, was three times as great as that observed during hypoxia. Although inosine and hypoxanthine were generally observed degradation products, adenosine was recovered only following uncoupled oxidative phosphorylation. Perfusion with 8-azaguanine, however, resulted in recovery of adenosine during both hypoxia and uncoupled oxidative phosphorylation. Washout studies demonstrated the rapid extracellular movement of adenosine and the total content of adenosine was uniformly greater in perfusates than in tissue. In no case was adenine nucleotide efflux observed nor phosphatase or deaminase activity in the perfusate demonstrated. In myocardium initial dephosphorylation to adenosine would appear to be the principal pathway of AMP degradation. The rapid extracellular movement of adenosine would justify its consideration as a mediator of metabolic control in the intact heart.