The effect of starvation on pancreatic insulin release was studied in vitro. A marked decrease in response to a glucose stimulus was present. Theophylline, tolbutamide, and dibutyrylcyclic AMP (DBcAMP) restored the insulin response to glucoseIn addition, the greater response to theophylline in starved compared with fed tissue suggests that 3’5’-cyclic AMP (cAMP) may be decreased in starvation. Inhibitors of glucose-stimulated insulin release such as diazoxide and epinephrine appear to have a different mechanism than starvation, although decreased availability of cAMP may also be involved. Of a variety of cyclic nucleotides tested, several others besides cAMP release insulin.