The effects of quisqualate and kainate on synaptosomal inositol phosphate (InsP) labelling, 45Ca influx and intrasynaptosomal free calcium ([Ca2+]i) were investigated. Each agonist caused a concentration-dependent increase in both [Ca2+]i and InsP labelling: quisqualate, however, produced significantly larger responses in both parameters and at lower EC50 values. Neither quisqualate or kainate significantly affected 45Ca influx into synaptosomes, indicating that the observed increases in [Ca2+]i were due to mobilisation from intracellular stores. The concentration-dependent increases in [Ca2+]i promoted by quisqualate and kainate were monophasic, whereas the increases in InsP formation fitted well to a biphasic curve. The EC50 values suggest that both kainate and quisqualate initially mobilise calcium from inositol 1,4,5-trisphosphate (Ins 1,4,5-P3)-sensitive stores and that the resultant increases in [Ca2+]i will, above a certain threshold, promote further increases in InsP production by stimulation of Ca(2+)-dependent phospholipase C. When saturating concentrations of kainate and quisqualate were used in combination, the effects on both InsP labelling and [Ca2+]i were not additive but were slightly higher than those produced by kainate alone: combined administration of the two agonists had no effect on 45Ca influx. These results suggest that kainate acts as a partial agonist at the presynaptic quisqualate metabotropic glutamatergic receptor.