Nociceptin, an endogenous ligand for the orphan receptor ORL₁, has recently been described. In this study we have shown that nociception inhibits 46 mM K⁺‐stimulated glutamate release from rat perfused cerebrocortical slices with an IC₅₀ of 51 nM. At 100 nM the inhibition amounted to 68 ± 14% and was naloxone (10 μm)‐insensitive excluding an activation of μ, δ and κ opioid receptors. These data demonstrate the functional coupling of ORL₁ in glutamatergic neurones and implicates a role for nociceptin in glutamatergic neurotransmission.