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The binding kinetics of the specific dopamine D₂ antagonist [³H]raclopride to dopamine D₂ receptors in rat neostriatum were studied. The pseudo-first-order rate constants of [³H]raclopride binding with these membranes revealed a hyperbolic dependence upon the antagonist concentration, indicating that the reaction had at least two consecutive and kinetically distinguished steps. The first step was fast binding equilibrium, characterized by the dissociation constant K_A = 12 ± 2 nM. The following step corresponded to a slow isomerization of the receptor-antagonist complex, characterized by the isomerization equilibrium constant K_i = 0.11. The dissociation constant K_d = 1.3 nM, calculated from these kinetic data, was similar to K_d = 2.4 nM, determined from equilibrium binding isotherm for the radioligand. Implications of the complex reaction mechanism on dopamine D₂ receptor assay by [³H]raclopride were discussed.