The metabotropic glutamate (mGlu) receptors, mGlu1 and mGlu5, mediate distinct inositol 1,4,5-trisphosphate (IP3) and Ca(2+) signaling patterns, governed in part by differential mechanisms of feedback regulation following activation. Single cell imaging has previously shown that mGlu1 receptors initiate sustained elevations in IP3 and Ca(2+), which are sensitive to agonist concentration. In contrast, mGlu5 receptors are subject to cyclical PKC-dependent uncoupling and consequently mediate co-incident IP3 and Ca(2+) oscillations that are largely agonist concentration-independent. Here, we have investigated the contribution of Gq/11alpha protein expression levels in shaping mGlu1/5 receptor-mediated IP3 and Ca(2+) signals, using RNA interference (RNAi). RNAi-mediated knockdown of Gq/11alpha almost abolished the single-cell increase in IP3 caused by mGlu1 and mGlu5 receptor activation. For the mGlu1 receptor, this unmasked base-line Ca(2+) oscillations that persisted even at maximal agonist concentrations. mGlu5 receptor-activated Ca(2+) oscillations were still observed, but were only initiated at high agonist concentrations. Recombinant over-expression of Gqalpha enhanced IP3 signals following mGlu1 and mGlu5 receptor activation. Interestingly, although mGlu5 receptor-mediated IP3 and Ca(2+) oscillations in control cells were largely insensitive to agonist concentration, increasing Gqalpha expression converted these oscillatory signatures to sustained plateau responses in a high proportion of cells. In addition to modulating temporal Ca(2+) signals, up- or down-regulation of Gq/11alpha expression alters the threshold for the concentration of glutamate at which a measurable Ca(2+) signal could be detected. These experiments indicate that altering Gq/11alpha expression levels differentially affects spatio-temporal aspects of IP3 and Ca(2+) signaling mediated by the mGlu1 and mGlu5 receptors.