Rp 49356, a 'K+ channel opener', inhibited 86Rb outflow, 45Ca outflow and insulin release from glucose-stimulated islets perifused in the presence of Ca2+. The drug lost its capacity to reduce 86Rb outflow in islets exposed to glucose-free or Ca(2+)-free medium. These observations suggest that RP 49356 might exhibit antagonistic actions on B-cell Ca2+ channels. This will, in turn, reduce glucose-stimulated insulin output and Ca(2+)-dependent 86Rb outflow.