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Basal levels of adenosine 3′, 5′-monophosphate (c-AMP) and the accumulation of c-AMP in liver in response to intravenous glucagon administered to Sprague-Dawley rats were studied in various states of nutrition, adrenal function and drug treatment. No major difference was observed in basal levels of c-AMP in fed and fasted rats. Glucagon produced a much greater rise in c-AMP in livers of fasted than fed rats. Refeeding the fasted rats for twenty-four hours decreased the response to glucagon; however, refeeding for three hours did not significantly change the increased responsiveness. L-tryptophan, but not tyrosine, pretreatment for three hours of the fasted rat produced a marked decrease in the response to glucagon. Adrenalectomy produced a decreased response of liver c-AMP to glucagon which was restored toward normal by cortisone treatment. The response of the liver to glucagon was markedly decreased by dihydroergotamine but not changed by dichloroisoproterenol or propranolol. Changes in blood glucose were in the same direction as changes in c-AMP but there was no close correlation.