In the submitted review the author pays attention to mechanisms of control of insulin secretion and the mutual interaction of other messengers (cAMP, calcium and inisitol triphosphate) with special attention to the calcium signal which plays a most important role in the stimulation of the excitable B cell. The trigger of the two-stage insulin secretion is cyclic accumulation of calcium in the cytosol of the B cell and the mutual harmony between calcium of the intra- and extracellular compartment. In the early stage of insulin secretion in particular the intracellular compartment is the source of calcium; from there the ion is released due to the action of inositol triphosphate (IP3) activated by phospholipase C. Calcium of the extracellular compartment is mobilized also in the early secretory stage by opening of the depolarization-dependent calcium channels, it plays, however, a more important part during the second stage. Activation of the other messengers, incl. the calcium signal, depends on the type of secretagogue stimulus. During systemic changes of calcium homeostasis in vivo the calcium signal of the B cell is activated or inhibited in different ways. In the course of hypercalcaemia, in particular if acute, the direct influence of calcium ions on insulin secretion is modulated by further factors, e.g. somatostatin, calcitonin, cholecystokinin, glucagon, adrenocortical hormones, opioids and other substances released into the blood stream. In chronic hypercalcaemia which is the result of primary hyperparathyroidism or vitamin D intoxication the action of calcium on the metabolic and hormonal response is enhanced by the ionophoretic action of parathormone or active vitamin D metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)