Pancreatic beta-cells secrete insulin in response to elevated blood glucose via Ca2+ dependent fusion of secretory granules with the plasma membrane (= regulated exocytosis). While exocytosis has been extensively investigated in rodent beta-cells, studies on human beta-cells are scarce. We have characterized the exocytotic properties of human beta-cells by capacitance measurements using the patch-clamp technique and carbon fibre amperometry. Voltage-clamp depolarizations evoked capacitance increases in single beta-cells in a time- and voltage-dependent manner. ~20% of the response occurred after the end of the depolarization pulse. Exocytosis was more dependent on Ca2+-influx through P/Q-type than L-type Ca2+-channels, reflecting the relative contribution of these channels to the total Ca2+-current. Exocytosis (as monitored by capacitance or amperometric measurements) decreased during repetitive stimulation, due to inactivation of Ca2+-channels as well as depletion of a readily releasable pool of granules. Capacitance measurements in beta-cells within intact islets revealed an additional, rapid component of exocytosis compatible with an immediately releasable granule pool. The beta-cell capacitance response was strongly amplified by elevation of intracellular cAMP levels. Somatostatin strongly depressed depolarization-evoked exocytosis.