The functional roles of anions on glucose-induced insulin secretion are poorly understood. We investigated the effects of the monovalent anions thiocyanate, iodide, bromide, nitrate and chloride on the dynamics of insulin secretion in isolated pancreatic islets from non-inbred Umeå ob/ob mice. All anion species (12 mM), except Cl-, significantly amplified glucose-induced (20 mM) first- and second-phase insulin secretion (selectivity sequence: SCN->NO3->I->Br->Cl-). Simultaneously, the anions reduced the lag-time prior to the initiation of the secretion (SCN-=I-=NO3->Br->Cl-). The results indicate that pancreatic beta-cell activation can be initiated and amplified by an anion-selective mechanism showing increasing degrees of activation in the order of the anion series of Hofmeister. On the basis of the strikingly similar anion selectivity of amplified secretion and shortened lag-phase, we suggest that both types of anion effects are caused by action at a single site on the beta-cell.