Acute hormonal regulation of fetal rat liver cyclic AMP content and glycogen phosphorylase activity was examined in an organ culture system using explants from term fetuses. Phosphorylase was rapidly activated by epinephrine and glucagon; the respective minimally effective concentrations were 2 X 10−7M and 10−8M. The characteristics of the adrenergic response were denned. Following the addition of a high concentration (10−5M) of epinephrine: Phosphorylase activity increased to a maximum at one minute (the earliest time point examined) and remained unchanged for at least 30 min; cyclic AMP levels were also maximally elevated by one minute but then declined over the next 30 min. The beta antagonist propranolol blocked both effects of epinephrine; the alpha antagonist phentolamine was without effect. The predominantly beta agonist isoproterenol was much more effective in elevating cyclic AMP levels and in activating phosphorylase than the predominantly alpha agonist phenylephrine. We conclude: i. fetal rat liver explants in organ culture offer a good in vitro model for studying acute hormonal regulation of glycogen metabolism; ii. the adrenergic receptor mediating the effects of epinephrine on fetal liver glycogen metabolism is of the beta type. (Endocrinology94: 935, 1974)