The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured with fura-2 in individual mouse pancreatic delta-cells identified by immunostaining for somatostatin. A majority of the delta-cells responded to 3 mM glucose with slow oscillations of [Ca2+]i (frequency, 0.1-0.4/min). In originating from a basal level of 60-100 nM and reaching peak values of 200-500 nM, the oscillations resembled those in insulin-secreting beta-cells stimulated by glucose. The rise in glucose to 20 mM resulted in a minor increase in the oscillatory frequency and sometimes in transformation of the oscillations into sustained elevation of [Ca2+]i. The addition of 3 microM L-epinephrine effectively counteracted the increase in [Ca2+]i in response to glucose. The delta-cells reacted with a sustained elevation of [Ca2+]i after raising extracellular K+ to 30.9 mM or adding 1 microM tolbutamide. Analyses using the patch-clamp technique revealed the presence of K+ channels with properties similar to the ATP-sensitive channels in pancreatic beta-cells. It is concluded that regulation of somatostatin release mimics that of insulin, with glucose induction of [Ca2+]i oscillations.