The effect of 1 hour of myocardial ischemia on the function of the stimulatory guaninenucleotide- binding protein G1was examined. This study follows our recent finding that myocardial ischemia increases the density of β-adrenoreceptors in a conscious canine model while having the opposite effect on the activity of adenylate cyclase. Coronary artery occlusion was induced in five conscious dogs and verified by measurement of blood flow using the Doppler and microsphere techniques. Alterations in the level and function of G1were examined in sarcolemmal membranes prepared from ischemic and nonischemic regions of the left ventricle. After 1 hour of coronary artery occlusion, the functional activity of sarcolemmal G1, as determined by reconstitution with eye" membranes, decreased by 27 ± 7% in the ischemic zone. Cholera toxin labeling performed in parallel with the reconstitution studies demonstrated a similar decrease of 28 ± 7%. This was associated with decreases in basal activity and decreases in adenylate cyclase activity stimulated by GTP, GTP phis isoproterenol, sodium fluoride, and forskoBn. Thus, a delect distal to the β-adrenoreceptor occurs in the transduction of adrenergjc signals to the heart as a consequence of 1 hour of ischemia.