Abstract: A ligand may be an agonist, activating the receptor, or an antagonist, blocking the receptor, or both, i.e. a partial (ant)agonist. Mechanistically, partial agonism could to be due to a binding interval longer than necessary for receptor activation. Then, the partial agonist would act as a full agonist during the activation interval and as a full antagonist thereafter. To test this hypothesis, the effects of different temperatures were evaluated in studies on electrically evoked [3H]-noradrenaline ([3H]-NA) release and in binding experiments at (predominantly presynaptic) α2-adrenoceptor sites, using rat neocortex and hippocampus slices and synaptosomes. The α2-autoreceptor-mediated inhibition of [3H]-NA release by a full (UK14304) and two partial (clonidine, guanfacine) agonists was tested in the absence and presence of autoinhibition. In addition, blockade of autoinhibition, i.e. the inhibitory effect of the endogenous full agonist NA, was analysed at different temperatures. In corresponding experiments, the binding to α2-adrenoceptor sites of [3H]-NA and the inhibition of this binding by UK14304, clonidine and guanfacine were evaluated. Concentration-inhibition curves of UK14304, clonidine and guanfacine in the absence of autoinhibition at 17 to 42°C revealed estimates of the concentrations of half maximum inhibition (IC50) and of the maximum inhibitions (Imax). IC50 and Imax values of UK14304 were not dependent on the temperatures applied. In contrast, the corresponding values of clonidine and guanfacine changed with temperature. At low temperature the partial agonists enhanced their antagonist properties. This was confirmed by the complete loss of the inhibitory effect of clonidine at 22°C in the presence of autoinhibition, i.e. when endogenous NA competed with the exogeneous ligand for the α2-autoreceptors. At 37°C, however, clonidine displayed agonist properties also in the presence of endogenous NA as UK14304 did at both 22 and 37°C. The disinhibition of [3H]-NA release, i.e. the blockade of autoinhibition, in the presence of the pure α2-adrenoceptor antagonists, idazoxan and rauwolscine, was the same at 22 and 37°C. The different influence of changing the temperature in the case of a full and of a partial agonist was confirmed in saturation and competition binding studies: Saturation binding Kds of the full agonist [3H]-NA were equivalent at high and low temperature; the Ki estimates of UK14304 were also independent of the temperatures applied, whereas Ki values of clonidine and guanfacine increased with lower temperatures. It is concluded that a full agonist is characterised by a short binding phase, just sufficient for receptor activation and smaller than the whole interval during which the receptor can be activated. The binding duration of a partial agonist, however, exceeds its activation interval at the receptor. Temperature reduction increases this excess of binding duration relative to the activation interval of a partial agonist.