The comparative glycogenolytic effects of cyclic N6-2'-O-dibutyryl-(DBC), inosine-(3',5'-IMP), cytidine-(3',5'-CMP), guanosine-(3',5'-GMP), thymidine-(3',5'-TMP), uridine-(3',5'-UMP) and 7-deaza-adenosine-3',5'-monophosphate (3',5'-pTu), and 5'-AMP, inosine and Ringer solution were studied in isolated perfused livers of fed rats. The compounds were infused in equimolar dosage (7.8 mmoles/hr)using a perfusate medium of either whole rat blood and Ringer solution (BLD) for 4 hr (62 experiments) or Krebs-Ringer bicarbonate (KRB) buffer for 150 min (29 experiments). A rank order of glycemic activity was observed, with DBC, 3',5'- pTu, 3',5'-IMP and its monobutyryl derivative showing greatest activity among the cyclic nucleotides tested. 3',5'-TMP, 3',5'-UMP, 3',5'- CMP, inosine and 5'-AMP did not significantly increase glucose compared to control perfusions with Ringer solution. 3',5'-GMP-induced hyperglycemia was significantly more than Ringer solution transiently and only in the KRB perfusate. The similar chemical structure of DBC, 3',5'-IMP and 3',5'-pTu suggests that a common receptor site for hepatic glycogenolysis may exist in rat liver.The results cast doubt on the specificity of 3',5'-AMP as the sole affector of hepaticglycogenolysis. {Endocrinology87: 377, 1970)