Glucose provokes a dose-related, rapid, sustained, and rapidly reversible reduction in the fractional outflow rate of 86Rb+ from perfused pancreatic islets. This efflux probably corresponds to a passive movement driven by the electrochemical gradient of K+ across the plasma membrane and mediated by a native ionphoretic system. Indeed, it is facilitated by valinomycin or cell membrane depolarization, little affected by ouabain, and inhibited by verapamil or omission of extracellular K+. The effect of glucose upon 86Rb+ efflux does not appear to be directly attributable to changes in either glucose transport, plasma cell polarization, Na+ influx, cyclic AMP concentration, or insulin secretion. Although a modulatory role of intracellular Ca2+ on K+ conductance cannot be ruled out, the experimental data suggest rather that the glucose-induced modification of 86Rb+ fractional outflow rate is directly linked, for its major part, to metabolic events such as an increase in the rate of glycolysis and/or generation of reduced pyridine nucleotides.