Changes in cytosolic free calcium concentrations ([Ca2+]i) in response to stimulatory glucose concentrations were investigated in human pancreatic islets, using Fura-2 fluorescence imaging. Increasing glucose concentration from 3 to 11 mM caused a triphasic [Ca2+]i response in human islets: an initial decrease (phase 1), a rapid and transient increase (phase 2) and periodic oscillations with a frequency of 1 +/- 0.3 min-1 (phase 3). Raising the glucose concentration from 11 to 16.7 mM lowered the frequency of the glucose-induced [Ca2+]i oscillations to 0.15 +/- 0.2 min-1, without changes in their amplitude. Human islet [Ca2+]i response to stimulatory glucose concentrations is synchronous throughout the islet. Freshly isolated human islets responded to tolbutamide (50 microM) with a rise in [Ca2+]i. An increase in glucose concentration, from 3 to 16 mM, in the presence of 100 microM diazoxide, produced a decrease in [Ca2+]i. It is concluded that human islets respond to glucose with regular [Ca2+]i oscillations that are synchronous throughout the islet and whose duration is modulated by glucose.