The central nervous system exerts a control on the endocrine pancreas and can modulate the basic feed-back loop linking the concentration of the main energy substrates in blood with islet cell functions. Thus, the elementary glucose-insulin system can be modulated under physiological conditions by both the long-recognized entero-insular axis and by a brain-islet axis, particularly when insulin release occurs in anticipation of meals. Experimental stimulation or section of afferent nerves to the pancreas have demonstrated the existence of this nervous control. Changes in islet cell secretion during stress illustrate this influence under clinical conditions. A variety of experimental data suggest intervention of the brain-islet axis under the physiological circumstances: 1) Manipulation of certain hypothalamic centres followed by modification of feeding behaviour and of islet secretion. 2) Input to the brain is both humoral (carried by arterial carotid blood or the cerebrospinal fluid) and nervous, of sensory and visceral origins. Changes in these afferent pathways may influence islet secretion via the efferent pathways of the vagus and splanchnic nerves. 3) Besides acetylcholine and catecholamines, peptide neurotransmitters are likely to be involved in the transmission of these nervous inputs to islet cells. 4) Furthermore, hypothalamic factor (s) may also modify the endocrine pancreatic secretions.