Selective activation of the two components of the sympatho-adrenal system (SAS) was produced by infusing male Sprague-Dawley rats with glucose or insulin. Intravenous glucose (0.5, 1 or 2 g/kg) raised plasma levels of glucose and insulin associated with a predominant activation of the sympathetic nervous system (SNS) as indicated by increased plasma norepinephrine (NE) levels. Glucose-induced release of NE was still seen in hypoinsulinemic, streptozotocin-treated rats but was absent after ganglionic blockade with chlorisondamine or following mannitol or saline infusions which failed to alter glucose or insulin levels. Insulin-induced (10 or 20 U/kg) hyperinsulinemia with its associated hypoglycemia produced predominant activation of the adrenal medulla producing increased plasma epinephrine (E) levels. But significant SNS activation also occurred with a concomitant increase in NE levels (14-22% of E) which appeared to be primarily from sympathetic nerves since increases still occurred following adrenal demedullectomy. Therefore, changes in plasma glucose levels alone and possibly altered intracellular concentrations or rates of glucose utilization can act as an important determinant of the pattern SAS activation although this may require pathological changes in plasma glucose levels to occur.