Insulin release is not a prerequisite for insulin synthesis in the pancreatic islets. Glucose is a strong stimulus for both synthesis and release of insulin. This stimulatory effect on insulin synthesis (and release) is enhanced by caffeine and dibutyryl cyclic AMP. Glucose—stimulated synthesis of insulin proceeds unabated even in the presence of diazoxide or of epinephrine or in the absence of calcium ion all of which are reported to inhibit insulin release. While the omission of magnesium ion from the incubation medium is reported not to affect the release of insulin stimulated by glucose, it nevertheless greatly depresses the biosynthesis of insulin. A small increase in insulin synthesis is noted in the presence of citrate. However, citrate does not enhance the effect of a submaximal concentration of glucose on synthesis. (Endocrinology92: 735, 1973)