The neuropeptide gastrin releasing peptide (GRP) stimulates insulin secretion and induces oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](cyt)) in clonal insulinoma cells. It is not known whether GRP affects [Ca2+](cyt) in normal beta cells. We investigated, in single, normal, mouse islet beta cells, the effects of GRP on [Ca2+](cyt) by dual wavelength spectrophotofluorometry. Beta cells were identified by their typical response to glucose or tolbutamide. At 15 mM glucose, GRP (100 nM) evoked an immediate [Ca2+](cyt), transient to 423 +/- 48 nM compared to 126 +/- 18 nM before GRP (P < 0.001). After the initial transient, [Ca2+](cyt) exhibited either a sustained elevation or oscillations. At 3.3 mM glucose, in cells with a non-oscillating [Ca2+](cyt), GRP stimulated a prompt increase in [Ca2+](cyt) (from 60 +/- 6 to 285 +/- 30 nM, P = 0.024) followed by either a sustained increase in [Ca2+](cyt) or [Ca2+](cyt) oscillations. We conclude that GRP promptly elevates [Ca2+](cyt) by a direct action in normal mouse pancreatic beta cells.