The increased insulin release induced by carbamoylcholine (CbCh) in pancreatic islets requires the presence of extracellular Ca2+. Intracellular recordings demonstrate that CbCh produces a transient increase in Ca2+ channel activity lasting from 30 to 60 s. Thereafter activity decreased to levels lower than in controls. When extracellular Ca2+ was present during this initial period, the stimulatory effects of CbCh were not different from those in which Ca2+ was present throughout. These experiments suggest that during muscarinic potentiation of insulin release extracellular calcium is only needed in the first minute.