Alterations in myocardial and plasma levels of adenosine 3′:5′-cyclic phosphate (cyclic AMP) were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic AMP levels increased markedly after thoracotomy but returned to control levels two hours later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham-occlusion. After localized coronary occlusion, only modest and insignificant changes occurred in plasma cyclic AMP levels in anesthetized animals and also in conscious dogs. The present study suggests that adrenergically mediated changes in tissue cyclic AMP content are an early manifestation of both generalized and local myocardial ischemia, while the plasma cyclic AMP level is a relatively insensitive indicator of small coronary occlusions.