Background and purpose: Several studies using radioligand binding assays, have shown that measurement of thermodynamic parameters can allow discrimination of agonists and antagonists (Weiland et al., 1979;Borea et al., 1996a). Here we investigate whether agonists and antagonists can be thermodynamically discriminated at CCK 2 receptors in rat cerebral cortex. Experimental approach: The pK L of [ 3 H]-JB93182 in rat cerebral cortex membranes was determined at 4, 12, 21 and 371C in 50 mM Tris-HCl buffer (buffer B pH 6.96; containing 0.089 mM bacitracin). pK I values of ligands of diverse chemical structure and with differing intrinsic activity (a), as defined by the lumen-perfused rat and mouse stomach bioassays, were determined in buffer B at 4, 12, 21 and 371C. Key results: [ 3 H]-JB93182 labelled a homogeneous population of receptors in rat cerebral cortex at 4, 12, 21 and 371C and the pK L and B max were not altered by incubation temperature. [ 3 H]-JB93182 binding reached equilibrium after 10, 50, 90 and 220 min at 37, 21, 12 and 41C, respectively. pK I values for R-L-365,260, R-L-740,093, YM220, PD134,308 and JB95008 were higher at 41C than at 371C. There was no effect of temperature on pK I values for pentagastrin, CCK-8S, S-L-365,260, YM022, PD140,376 and JB93242. Conclusions and implications: CCK 2 receptor agonists and antagonists at rat CCK 2 receptors cannot be discriminated by thermodynamic analysis using [ 3 H]-JB93182 as the radioligand.