Oscillatory signaling and insulin release were studied in isolated pancreatic islets and beta-cells obtained from human cadaveric organ donors. Taking advantage of Sr2+ as an analog for Ca2+, it was possible to demonstrate glucose-induced rhythmic activity in individual beta-cells identified by immunostaining. Glucose-induced slow oscillations of Sr2+ (frequency, 0.1-1.0/min) were sometimes seen at a sugar concentration as low as 3 mM. Addition of 20 nM glucagon resulted in a broadening of the oscillations or in their transformation into sustained elevation. Moreover, the presence of glucagon resulted in the appearance of short transients of Sr2+, which disappeared after exposure to the intracellular Ca2+-adenosine triphosphatase inhibitor thapsigargin. Digital image analyses indicated that slow oscillations can be synchronized among cells in small aggregates and intact islets. The rhythmic activity in the glucose-stimulated beta-cell had its counterpart in pulsatile insulin release when single islets were perifused with a Sr2+-containing medium. It is concluded that the human beta-cell has oscillatory signaling for insulin release similar to that observed in experimental animals.