Tolbutamide and diazoxide, which respectively decrease and increase the activity of ATP-sensitive K+ channels, were used to investigate whether these channels play a role in the control of glucose-induced electrical activity (slow waves with spikes) in pancreatic B-cells. Addition of tolbutamide to a medium containing 10 mM glucose largely mimicked the effects of a rise in glucose concentration from 10 to 15 mM on electrical activity, ionic fluxes and insulin release. Tolbutamide was still active in the presence of maximally effective concentrations of glucose (30-40 mM). Diazoxide restored slow waves of membrane potential in B-cells which were persistently depolarized by 30 mM glucose. It is concluded that ATP-sensitive K+ channels are still operative at high glucose concentrations. These channels could thus be one target on which physiological concentrations of glucose act to regulate electrical activity in B-cells and, hence, insulin release.