In normal pituitary cells somatostatin (SRIF) blocks the spontaneous oscillations in [Ca++]i by inhibiting the generation of action potentials. This is sufficient to explain the inhibitory effect on basal, but not entirely that on stimulated pituitary hormone secretion. In insulin secreting cells, which, in contrast to pituitary cells, only fire action potentials on stimulus-evoked depolarization, SRIF hyperpolarization and lowering of [Ca++]i is only transient. The marked inhibition of insulin secretion is suggested to be due to a coordinated action of SRIF on membrane potential and [Ca++]i as well as a direct interference with late secretory events.