The mechanisms by which glucose and other stimulators control the rate of insulin release from the/3-cells of islets of Langerhans is still far from understood. In general terms, it is assumed that a receptor for a glucose metabolite is the initiator of interactions leading to increased insulin release. These interactions may involve cyclic AMP, Ca++, cytosol components, microfilaments and microtubules, the insulin containing granule membranes and the Ncell plasma membrane, and lead to fusion of granule membranes with the plasma membrane and the release of insulin from the cell. This short review concentrates on the adenylate cyclase system including the enzyme, its product cyclic AMP, cyclic nucleotide phosphodiesterases which break down cyclic AMP, effector systems for cyclic AMP such as protein kinases and phosphoprotein phosphatases. Inevitably, the interaction with glucose will be an important theme in the discussion because (a) cyclic AMP" potentiates" the insulin-releasing capability of glucose and (b) glucose increases the intracellular concentration of cyclic AMP in islets of Langerhans. Knowledge that cyclic AMP enhances the/3-cell response to glucose came from the demonstration that glucagon increased insulin secretion and that the response to glucagon was greater during hyperglycaemia that at normal glucose levels [1-4]. By analogy with the effect of glucagon in stimulating adenylate cyclase in liver, it was suggested that cyclic AMP was involved in the mediation of these effects. Since that time, many reports have confirmed the effects of glucagon on insulin release, and the similarities of action between those agents which raise intracellular cyclic AMP levels, such as glucagon,/3-adrenergic agents, phosphodiesterase inhibitors (papaverine, methylxanthines) and cholera toxin, and the effects of exogenous cyclic AMP or dibutyryl cyclic AMP have been noted [5-14]. It is clear from these reports that when the cyclic AMP concentration of the/3-cell is raised, by whatever means, the insulin response to glucose stimulation is enhanced. It is also clear that the effects of cyclic AMP are greatest at high glucose concentrations, whereas at low, non-stimulatory glucose concentrations the effects of cyclic AMP are usually small.