At intermediate glucose concentrations, [Ca2+]i (intracellular calcium) measured in single islets of Langerhans undergo oscillations that are caused by glucose-induced bursting of electrical activity. Using digital video imaging of fura-2--loaded islets, we have analyzed the spatial distribution of [Ca2+]i in response to the natural secretagogue glucose and the KATP channel blocker tolbutamide. When the glucose level is increased, [Ca2+]i first increases and then starts to oscillate with a synchronous pattern through the islet. The synchrony is maintained even during nonrhythmic oscillatory patterns. In the presence of tolbutamide, [Ca2+]i increases in all the islet regions, suggesting that the calcium signal is derived mainly from the beta-cell population. These results demonstrate that the islets behave as a functional syncytium in response to stimulatory glucose levels, canceling out heterogeneities at the single cell level.