Insulin-induced hypoglycemia and the subsequent administration of glucose were examined for their effects on single unit activity of locus coeruleus noradrenergic (LC-NE) neurons in unanesthetized, unrestrained cats. LC-NE neuronal activity showed an inverse relationship to blood glucose levels. The activity of most cells increased during sustained hypoglycemia, and then decreased following glucose administration. Some neurons were unaffected by hypoglycemia, but were inhibited following glucose. The activation of LC-NE neurons in response to insulin administration generally paralleled the increase in plasma epinephrine, although the adrenal response was more sensitive. These data, together with those reported in the preceding papers, suggest the following general conclusions: (1) physiological stimuli can influence the activity of LC-NE neurons in unanesthetized subjects (although they do so less strongly than environmental stimuli); (2) these effects of physiological stimuli upon LC-NE neurons can be exerted independent of changes in behavioral state; (3) LC-NE neurons do not appear to play a specific role in the regulation of any of the systems examined, but may instead play a more global role in the response to physiological challenges in general; (4) LC-NE neurons are generally co-activated with both the neural and hormonal components of the sympatho-adrenal system, although sympathetic activation can occur in the absence of increased LC-NE activity. A previously hypothesized role for LC-NE neurons in facilitating the behavioral response to environmental stressors may thus be extended to include the response to physiological challenges, and perhaps facilitation of the physiological as well as the behavioral components of the stress response.