Various pharmacological compounds, reserpine, propranolol, hydroquinidine, procaine, verapamil, atropine and nicotinic acid were tested for their ability to modify the glucagon plasma concentration in normal rats both in the basal state and after stimulation by exercise or insulin administration. These drugs were selected on the basis of their known effect on the autonomous nervous system, on transmembrane sodium or calcium fluxes or on the level of plasma free fatty acids. Basal plasma glucagon level was significantly increased 24 hr after administration of reserpine and conversely it was decreased 60 min after administration of hydroquinidine, procaine and atropine. The exercise-induced rise in plasma glucagon which was previously shown to be inhibited by propranolol was not affected by the tested substances with the exception of nicotinic acid. Indeed, blockade of the rise in plasma free fatty acids normally associated with exercise, result in a significantly greater increase in glucagon plasma concentration in animals treated by nicotinic acid. Insulin-induced hypoglycemia provoked a 6-fold increase in plasma glucagon concentration, this rise was not altered by reserpine, hydroquinidine, procaine nor verapamil. It was increased by propranolol which slightly potentiated the hypoglycemie effect of insulin as well as by nicotinic acid which accentuated the depression in plasma free fatty acid induced by insulin. The most striking change was that atropine reduced by about 50 per cent the rise in plasma glucagon secondary to insulin administration. In view of these results, it would be of interest to study the behaviour of plasma glucagon concentration in patients chronically treated with atropine, hydroquinicline or procaine analogs in their respective and already established therapeutic uses.