Oscillations in intracellular free calcium concentration (Ca(2+)) occur spontaneously in immature neurons of the developing cerebral cortex. Here, we show that developing murine cortical neurons exhibit calcium oscillations in response to direct activation of the mGluR5 subtype of the group I metabotropic glutamate receptor (mGluR). In contrast, other manipulations that elicit Ca(2+) increases produce simple, nonoscillatory changes. Furthermore, we find that spontaneous oscillatory Ca(2+) activity is blocked by antagonists of group I mGluRs, suggesting a specific role for mGluR activation in the promotion of oscillatory Ca(2+) dynamics in immature cortical neurons. The oscillatory pattern of Ca(2+) increases produced by mGluR activation might play a role in the regulation of gene expression and the control of developmental events.