The effect of single (1.4 and 24 h) and long-term (7 days) hydrocortisone intramuscular administration (5 mg/100 g of body mass) on 5'-nucleotidase and adenosine deaminase activities in homogenate and subcellular fractions of the rat brain hypothalamus and hippocampus has been studied. Enzymatic activity of adenosine metabolism in hypothalamus and hippocampus has been shown to undergo changes with the duration of hydrocortisone administration. A possible role of adenosine in the mechanism of glucocorticoid action in the CNS and the regulation of the hypothalamic-pituitary-adrenal axis is under discussion.