The influence of adrenergic agents, epinephrine and clonidine, on plasma immunoreactive insulin and plasma glucose concentrations was studied in mice. Subcutaneous injection of epinephrine in fasted mice did not alter the plasma glucose concentration (PG), while plasma immunoreactive insulin concentration (IRI) tended to increase gradually. Intravenous injection of glucose markedly increased IRI. Glucose-induced IRI increase was inhibited by a subcutaneous injection of epinephrine in spite of high elevation of PG. This inhibition of glucose-induced IRI increase by epinephrine was reversed after treatment with an alpha-adrenergic blocking agent, phentolamine. Propranolol, an beta-adrenergic blocking agent suppressed IRI to a greater extent as compared with IRI induced by simultaneous injection of glucose and epinephrine. These results indicate that beta-adrenoceptor stimulating action accelerates the insulin release induced by glucose while alpha-adrenoceptor stimulating action inhibits it. Subcutaneous injection of clonidine in fasted mice slightly decreased IRI and increased PG. The response of PG to clonidine was dose-dependent. Glucose-induced IRI increase was inhibited by an intravenous injection of clonidine, and PG was elevated under the same conditions. The inhibition of glucose-induced IRI increase by clonidine was reversed when phentolamine was given, and under these conditions, PG showed no change. Propranolol treatment did not result in a recovery of the inhibition of glucose-induced IRI increase by clonidine. When compared with the results of epinephrine treatment, it may be concluded that clonidine shows alpha-adrenoceptor stimulating action in the secretion of insulin from beta-cells of the endocrine pancreas.