The effects of adrenalectomy and of cortisol on the plasma amino acids of eviscerated animals were studied using alloxan-diabetic rats. The hourly changes in plasma amino nitrogen were followed for periods up to 6 hr after evisceration. Cortisol was given either at the time of evisceration or for various times (1-12 hr) beforehand. It was found: 1) The rise in plasma amino nitrogen of diabetic rats was markedly reduced by adrenalectomy. 2) Cortisol restored and increased the rate of rise of plasma amino acids of adrenalectomized-diabetic rats.3) The administration of cortisol to adrenalectomized-diabetic rats at various times before evisceration did not alter the rate of increase of plasma amino nitrogen following evisceration when allowance was made for the total time of exposure to the hormone. 4) There was a significant delay of about 2 to 3 hr before the effects of cortisol on the plasma amino nitrogen could be detected. It is concluded that the effects of glucocorticoids on gluconeogenesis cannot be due solely to an effect on the liver itself but are in large part a consequence of their ability to increase the rate of release of amino acids from the extrahepatic tissues. (Endocrinology 80: 561, 1967) T HE METABOLIC effects of cortisol and allied steroids on the carbohydrate and protein metabolism of fasted normal, adrenalectomized or hypophysectomized animals can be divided into two components (1). These are (a) a catabolic effect on the tissue proteins by which the rate of release of amino acids into the blood is increased and (b) an anabolic effect on the liver by which the excess of amino acids is converted by this organ into glucose and glycogen.It is still unsettled whether these effects on tissue protein breakdown are a consequence of a primary catabolic effect of these hormones on all tissue proteins with secondary stimulation of hepatic gluconeogenesis or whether they are a result of a primary stimulation of hepatic gluconeogenesis which in turn evokes an increased release of tissue amino acids. A third possibility is, of course, that the hormones stimulate simultaneously both these processes.In an attempt to clarify the relative importance of the liver and the extrahepatic tissues in the alterations in protein and carbohydrate metabolism that follow adrenalectomy or the administration of excess adrenal cortical steroids (1, 2), the effects of these procedures on the carbohydrate 1 and protein metabolism of eviscerated rats have been reinvestigated with certain changes in the experimental design that seemed to be called for in the light of past experience with such preparations. In the first place, alloxan-diabetic rats were used for adrenalectomy and subsequent evisceration so that residual insulin would not obscure the possible effects of steroid treatment. Second, microchemical techniques were used so that serial sampling did not produce excess loss of blood. The rate of increase in plasma amino acids after evisceration could then be used to follow the time course and magnitude of the response...