Both alpha- and beta-D-glucose pentaacetate (1.7 mM each) augmented, to almost the same extent, insulin release caused by succinic acid dimethyl ester (10.0 mM) in rat pancreatic islets. The secretory response to these hexose esters largely exceeded that evoked by unesterified D-glucose tested at the same concentration (1.7 mM). The release of insulin provoked by succinic acid dimethyl ester was inhibited, however, by alpha-D-galactose pentaacetate, whilst being unaffected by beta-D-galactose pentaacetate (each also 1.7 mM). It appears, therefore, that the insulinotropic action of hexose esters is not attributable solely to the catabolism of their carbohydrate moiety, but may also involve a receptor system that displays anomeric specificity and can be directly activated or inhibited by the esters themselves. Hence, it is proposed that selected esters of non-nutrient monosaccharides may represent new tools to either stimulate insulin release in diabetes or prevent excessive hormonal secretion in situations of hyperinsulinemia.