Normal men and women were infused with the π-adrenergic receptor stimulator, isoproterenol (isopropylnorepinephrine, Isuprel). At a low dose (2 μg./min.), immunoreactive insulin (IRI) and free fatty acid (FFA) concentrations rose without a measurable change in plasma glucose. The rise in IRI was not blocked by pretreatment with nicotinic acid to prevent FFA mobilization by isoproterenol. Higher doses of isoproterenol (6 μg./min.) caused larger increments of IRI and FFA concentrations but also elevated plasma glucose. All effects of isoproterenol were the β-adrenergic receptor DlocKing agent y propranolol. Propranolol had no effect on glycogenolysis or IRI stimulation by glucagon. It is concluded that isoprotenol inereases IRI levll by direet seimnlation of β-adrenergic receptors. The ability of glucagon to stimulate the pancreatic islet and to elevate IRI appears to be mediated by a different mechanism.