This study tested quantitatively the degree to which selective activation of NMDA receptors increases the intracellular concentration of free Ca 2 + ions ([Ca 2 + ] i ) in neurons isolated from the rat spinal cord dorsal horn and grown in culture. The results show that activation of NMDA receptors, without additional depolarizing stimuli, produce [Ca 2 + ] i increases in the neuronal cell bodies in the presence of physiological concentrations of Mg 2 + . Furthermore, this phenomenon occurs during synaptic activation of NMDA receptors. Thus, it cannot be assumed that in physiological extracellular [Mg 2 + ], there is an absolute requirement for additional membrane depolarization before NMDA receptor activation stimulates significant increases in [Ca 2 + ] i .