Cyclic AMP (cAMP)-dependent stimulation of neutral and dibasic amino acid uptake by intestinal mucosa was investigated by the use of everted intestinal rings, β-adrenergic receptor sites on the mucosal cell itself were implicated, since epinephrine and isoproterenol stimulated uptake in vitro, which was blocked by propranolol. Glucagon, vasopressin and norepinephrine had no effect on tissue cyclic AMP levels or on amino acid uptake but cholera toxin given in vivo increased both parameters tested in vitro. Theophylline and isoproterenol caused an increase in cyclic AMP levels in the villus tip cells, where these drugs also stimulated amino acid uptake. Neither drug increased cAMP in crypt cells. Thus, the cyclic AMP-stimulated uptake of amino acids in vitro is a function of the villus tip cells. Moreover, when metabolic products, such as cAMP, are measured in whole intestinal mucosa, it cannot be assumed that the change is uniform throughout the tissue, but may involve only one type of cell on the intestinal villus.