Intrasynaptosomal free calcium concentrations measured in rat cortical synaptosomes using the calcium sensitive fluorescent dye quin 2, were found to be 0.107-0.122 microM (n = 33). Stimulation of alpha 2-adrenoceptors or kappa-opiate receptors with clonidine (0.1-100 microM) or dynorphin A fragment (1-13) (0.2-5.0 microM) respectively, produced a dose dependent reduction in the intrasynaptosomal free calcium concentration. The alpha 2-adrenoceptor mediated reduction produced by clonidine (100 microM) was antagonised by the selective alpha 2-antagonist idazoxan (RX781094) (200 microM). Dynorphin A-(1-13) (1 microM) caused a reduction which was antagonised by a high (20 microM) but not low (2.0 microM) concentration of naloxone. We conclude that unlike the mu- and delta-opiate receptor, stimulation of alpha 2-adrenoceptors or kappa-opiate receptors elicits changes in intrasynaptosomal free calcium concentration which are independent of the voltage sensitive calcium channel. This does not preclude the possibility that the alpha 2-adrenoceptor and kappa-opiate receptor also have an effect at the voltage sensitive calcium channel.