The secretory responses of beta and delta cells were compared in the isolated, perfused, rat pancreas. Insulin release was stimulated 50-fold and somatostatin (SRIF) secretion twofold when the glucose concentration was increased from 100 mg/dl to 300 mg/dl. When islet cyclic AMP (cAMP) was raised by 3-isobutyl-1-methylxanthine (IBMX), the secretion of SRIF was stimulated in a glucose-dependent manner (300 mg/dl greater than 100 mg/dl greater than 25 mg/dl). As expected, insulin release was also potentiated in a similar fashion. A difference in the glucose dependency of the cAMP effect was seen at 25 mg/dl glucose, where 0.25 mM IBMX enhanced the release of SRIF but not that of insulin. In contrast, at 300 mg/dl glucose, IBMX caused a greater potentiation of insulin release than of SRIF release. The release of insulin, when expressed in absolute terms, was stimulated more markedly than that of SRIF under most conditions tested. However, the expression of total hormone released during 30 min of stimulation as a percentage of tissue hormone content allowed a different interpretation of the results. For example, 2.1% and 1.8% of tissue insulin and SRIF contents, respectively, was released during exposure to 300 mg/dl glucose. Surprisingly, under basal conditions (100 mg/dl glucose), 1.0% of total SRIF content was released during 30 min compared with the release of only 0.04% of insulin.