We examined the effects of a single intravenous injection of homologous islet amyloid polypeptide (IAPP) on the plasma levels of glucagon, insulin and glucose in the freely fed mouse. It was observed that IAPP suppressed basal glucagon levels concomitant with a decrease of the blood glucose concentrations. Basal plasma insulin levels were not affected. IAPP did not appreciably modulate the plasma concentration of glucose, insulin or glucagon after an intravenous glucose load. Further, IAPP inhibited the insulin secretory response to beta 2-adrenoceptor stimulation. IAPP also lowered the plasma glucagon levels following beta 2-adrenoceptor stimulation, whereas no apparent effect on plasma levels of glucose was observed. The data suggest that IAPP suppresses glucagon secretion and lowers blood glucose levels in the freely fed mouse. It might also exhibit a negative feedback inhibition on beta 2-adrenoceptor-induced insulin secretion, but has little influence on glucose-induced insulin release. Since IAPP is co-secreted with insulin, it is not inconceivable, that in the freely fed mouse, IAPP may act to amplify the blood glucose lowering effect of insulin through a direct suppression of glucagon secretion via the islet microcirculation.